receptor

A protein or cell that can detect an incoming stimulus.

signal transduction pathways
Biochemical pathways in which a change in
conformation of a receptor protein in the target cell is
converted to a change in the activity of that cell.
paracrine
A type of chemical messenger that is involved in local
signaling between nearby cells; paracrine
messengers move through the interstitial fluid by
diffusion.
autocrine
A type of cell signaling in which a single cell signals
another cell of the same type, including itself.

preprohormone
Large inactive polypeptide that is a precursor to a
peptide hormone
prohormone
A polypeptide formed by the cleavage of a
preprohormone; a precursor to the formation of a
peptide hormone.
half-life
A period of time required for half of a population of
molecules to be converted to another form; often
applied to radioactive decay.
transmembrane receptor
A receptor protein that spans the cell membrane;
consists of an extracellular domain, a transmembrane
domain, and an intracellular domain.

endocrine system
The collective name for the group of glands and other
tissues that secrete hormones into the circulatory
system

ligand
A chemical that specifically and reversibly binds to a
receptor or enzyme.

nervous system
Network of neurons and their supporting cells.

mineralocorticoids
Steroid hormones involved in water and ion balance.

hormone
Type of chemical messenger that is carried in the
blood and thus can act across long distances.
Classically defined as a substance released from an
endocrine gland and active at very low
concentrations.

glucocorticoids
Steroid hormones involved in the stress response that
regulate carbohydrate, protein, and lipid metabolism.

neurotransmitter
A chemical messenger released from a neuron into
the synaptic cleft.
gap junctions
Aqueous pore between two cells that allows ions and
small molecules to move freely from cell to cell;
formed by proteins called connexins in the vertebrates
and innexins in the invertebrates.
synapse
The junction between a neuron and another neuron or
effector cell; consists of a presynaptic cell, the
synaptic cleft, and a postsynaptic cell.
pheromones
Chemical messengers released by an animal into the
environment that have an effect on another animal of
the same species.
neurohormone
A chemical messenger released from a neuron into
the blood.
gland
A specialized organ that secretes hormones.
cytokines
Hormones that trigger cell division.

carrier protein
Blood proteins that help to transport hydrophobic
molecules (such as steroid hormones) in the blood.
albumin
A binding globulin (carrier protein) that is one of the
primary proteins of vertebrate plasma; makes a major
contribution to blood osmotic pressure.

amine
A class of molecules based on ammonia, with a side
group substituting for at least one N atom.
biogenic amine
A class of neurotransmitters derived from amino acids
including the catecholamines and dopamine.
catecholamines
The biogenic amines epinephrine and norepinephrine.
dopamine
A neurotransmitter (biogenic amine) produced in
various regions of the vertebrate brain.
norepinephrine
A catecholamine neurotransmitter; in vertebrates,
released by the sympathetic nervous system.
epinephrine

A catecholamine that can act as a hormone or

neurotransmitter and is involved in the stress
response; also called adrenaline.

A decrease in the amount or activity of a protein or

process; e.g., a decrease in receptor number or
activity on a target cell

thyroid hormone
An iodine-containing hormone produced by the
thyroid gland that is involved in the regulation of
metabolism.

up-regulation
Increase in protein number or activity in a target cell

serotonin
A neurotransmitter (biogenic amine) involved in
setting mood and regulating blood flow to the brain.
melatonin
A hormone found in all animal groups that regulates
sleep-wake cycles.
histamine
An amino acid; a regulatory molecule that is released
from mast cells in response to an immunological
challenge.
acetylcholine
A neurotransmitter found in most animal species in
many types of neurons, including motor neurons and
the autonomic ganglia of vertebrates.
eicosanoids
A type of short-lived chemical signaling molecule.

nitric oxide
A gaseous neurotransmitter and paracrine chemical
signal that is involved in regulating many physiological
processes; important vasodilator in vertebrates.
agonist
A substance that binds to a receptor and initiates a
signaling event. May include both the natural
endogenous ligand as well as pharmaceutical agents
that mimic the natural substance.
antagonist
A substance that binds to a receptor but does not
stimulate a signaling event. __________s interfere
with the binding of the natural ligand.
down-regulation
A short-lived intracellular messenger that acts as an
intermediate in a signal transduction pathway.
cyclic AMP
A second messenger produced by adenylate cyclase;
most important action is the stimulation of protein
kinase A.
inositol triphosphate (IP3)
A second messenger in the phosphatidylinositol
signaling system.

dissociation constant (Kd)

A measure of the tendency of a complex to dissociate
into its components; calculated as the ratio of the
product of the concentrations of the dissociated
components to the concentration of the complex once
the reaction reaches equilibrium (e.g., for the reaction
AB <-> A + B, Kd = [A][B]/[AB]).
affinity constant (Ka)
Reciprocal of the dissociation constant.
ligand-gated ion channel
An ion channel that opens or closes in response to
the binding of a specific chemical.
G-protein-coupled receptor
A transmembrane receptor that interacts with a G
protein.
G protein
Type of trimeric membrane protein, associated with
specific transmembrane receptors, that plays a role in
signal transduction. __________s bind guanine
nucleotides; when bound to GDP the G protein is
inactive, but when bound to GTP it is active. The
alpha subunit of the G protein moves through the
membrane and acts in subsequent steps in the signal
transduction pathway.
second messenger
A short-lived intracellular messenger that acts as an
intermediate in a signal transduction pathway.
orphan receptors
Receptors whose ligand and function is not known;
identified based on structural similarity to known
receptors.
calmodulin
A calcium-sensing protein involved in many signal
transduction pathways.
Second messenger
A short-lived intracellular messenger that acts as an
intermediate in a signal transduction pathway.
diacylglycerol (DAG)
A second messenger in the phosphatidylinositol
signaling system.
set point
In a homeostatically controlled system, the level at
which the regulated variable is maintained.
anterior pituitary gland
The anterior lobe of the pituitary gland of vertebrates,
also called the adenohypophysis; secretes tropic
hormones.

posterior pituitary
Lobe of the pituitary gland; secretes antidiuretic
hormone and oxytocin; also called the
neurohypophysis.
hypothalamic-pituitary portal system
A system of blood vessels within the hypothalamus
and pituitary that carries hypothalamic hormones to
the pituitary, where they regulate the release of
pituitary hormones.
tropic hormones
Hormones that cause the release of other hormones.
insulin
Peptide hormone that homeostatically regulates blood
glucose levels; released in response to increased
blood glucose.
pancreas
A vertebrate organ that produces endocrine hormones
including insulin and glucagon and also produces
exocrine secretions that are involved in digestion.
islets of Langerhans
Clusters of endocrine cells in the pancreas that
produce the hormones glucagon and insulin.
pancreatic cells
Cells within the vertebrate pancreas that secrete the
hormone insulin.
glucagon
A hormone produced by the vertebrate pancreas that
inhibits glycogen synthesis and stimulates glycogen
breakdown, resulting in an increase in blood glucose.
epinephrine
A catecholamine that can act as a hormone or
neurotransmitter and is involved in the stress
response; also called adrenaline.
adrenal gland
A gland near the kidney, which in mammals is
composed of an outermost layer (the adrenal cortex)
and an inner layer (adrenal medulla).
adrenal cortex
Outermost layer of the adrenal gland.
adrenal medulla
Inner layer of the adrenal gland.
chromaffin cells
Cells that secrete the hormone epinephrine
(adrenaline). In mammals they are located in the
compact adrenal medulla, but in other vertebrates
they are more dispersed.

What are the three major steps involved in indirect

chemical signaling?
First, a chemical signal is released from the
signaling cell into the extracellular environment.
Second, the chemical signal is transported through
the extracellular environment to the target cell.
Third, the chemical signal binds to a receptor on the
target cell, thus communicating the signal.

Would you expect the chemical signaling molecules

involved in signaling via gap junctions to be
hydrophilic or hydrophobic? Justify you answer.
Hydrophobic molecules can cross the lipid bi-layer
of membranes and therefore do not require gap
junctions to be transferred between cells.
Hydrophilic molecules cannot cross these
membranes, and therefore require gap junctions
that create aqueous pores between cells, therefore
allowing the transfer of hydrophilic molecules
between cells.

Compare and contrast autocrine, paracrine,

endocrine, and neural communication.
Autocrine: The chemical signals affect the cell that
secreted it (signaling cell).
Paracrine: The chemical signals diffuse in the
extracellular environment and affect cells in the
immediate surrounding of the signaling cell.
Endocrine: The chemical signals (called hormones)
are transported long distances by the circulatory
system.
Neural: First, electrical signals are transported long
distances along an individual cell (a neuron).
Second, the electrical signal is either directly
transmitted to a target cell, or triggers the release of
chemical signals (neurotransmitters) that travel a
short distance to affect the target cell.

You read an article in the newspaper about the

discovery of a new steroid hormone. What can you
predict about how it is synthesized and/or stored by
the signaling cell, how it is transported through the
blood, and how it acts on the target cell? If the
newspaper article were about a peptide hormone,
how would your predictions change?
All steroid hormones have a number of
characteristics in common:
Steroid hormones are cholesterol derivatives and
synthesized in the smooth endoplasmic reticulum or
mitochondria. Because, as lipids, they can easily
cross membranes, they cannot be stored in cells
are therefore synthesized on demand. As lipids,
they are also hydrophobic and require to be bound
to carrier proteins when transported in blood. Like
other lipophilic hormones, steroids will bind to
intracellular receptors of target cells and promote
gene transcription, although in some cases steroids
can bind to transmembrane receptors and trigger
non-genomic effects.

Peptide hormones are composed of amino acids

assembled in a precise sequence. They are
therefore synthesized in the rough endoplasmic
reticulum where ribosomes translate an mRNA into
a peptide. Peptides are not lipid soluble and
therefore cannot cross membranes. Once
synthesized, they are stored in cellular vesicles,
which release their content in the extracellular
environment by exocytosis when needed. Because
they are hydrophilic, peptides do not require to be
bound to a carrier molecule to be transported in the
circulatory system. Once they reach a target cell,
they bind to transmembrane receptors, as they
cannot cross the membrane of the target cell.

How do selective serotonin reuptake inhibitors

(SSRIs) affect the response of a target cell to
serotonin?
Normally, neurotransmitters (such as serotonin) are
removed from synapses shortly after being
released by the reuptake of surrounding cells.
Chemicals, called reuptake inhibitors, can inhibit
the process of reuptake. By keeping more of the
neurotransmitters in the synapse, for a longer
period, there is an increase in the binding of the
neurotransmitter to its receptor on the target cell.

What is the difference between a neurohormone

and a neurotransmitter?
Neurotransmitters refer to chemical messengers
secreted by neurons in a synapse where they
diffuse a very short distance to the target cell.
Neurohormones refer to chemical messengers
secreted by neurons in the circulatory system; they
act like hormones and are secreted by neurons.

From the perspective of the target cell, is there a

fundamental difference between a paracrine signal
and an endocrine siganal? Why or why not?
As far as the target cell is concerned, there is no
difference between the two. For both types of
communication systems, the binding of a chemical
signal to the target cell's receptor will lead to
changes in the function of the target cell.

List the main classes of chemicals involved in

indirect cell signaling in animals. Which of these
classes are utilized for endocrine communication?
Peptides, Steroids, Amines, Lipids, Purines, Gases.
Of these, only peptides, steroids, and amines act as
hormones in the endocrine system.

Why are peptide messengers released by

exocytosis?
Peptide synthesis can be slow because it involves
the complex process of gene transcription. Once
synthesized, peptides cannot leave the signaling
cell because they are hydrophilic and cannot cross
membranes. By being synthesized in advance and
stored in vesicles, peptide messengers can be
released in the extracellular environment on
demand by signaling cells.

What are the three main domains of a

transmembrane receptor, and what are their
functions?
The ligand-binding domain (on the external surface
of the membrane) can specifically bind to a
chemical messenger. When binding of a ligand
occurs, the transmembrane domain (within the
membrane) can activate the catalytic domain (on
the internal surface of the membrane), which acts
as an enzymatic catalyst that triggers the next steps
of the signal transduction cascade.

Describe the phenomenon of "endocrine

disruption".
Some synthetic chemicals have structures that are
similar enough to natural hormones that they can
bind to cellular receptors, thus mimicking or
inhibiting the action of the natural hormone. A
typical example of this is that the insecticide DDT
can bind to steroid hormone receptors, leading to
reproductive and development abnormalities in
animals exposed to this chemical in their
environment.

Compare and contrast the functions of intracellular

and transmembrane steroid receptors.
When steroid hormones cling to intracellular
receptors, the process of gene transcription in
initiated, which will lead to slow changes in cellular
function (it takes time to synthesize new proteins).
When steroid hormones bind to transmembrane
receptors, a cytoplasmic signal transduction
pathway will be initiated, which lead to faster
changes in cellular function.

How do the thyroid hormones differ from all of the

other biogenic amines?
Thyroid hormones differ from other biogenic amines
by being lipid soluble, which means that they are
more similar to steroids in the way they are
transported in the circulatory system (bound to
carrier proteins) and in the way they change the
function of target cells (triggering of gene
transcription).

What would be the effect of increasing receptor

number on the response of a target cell to the
ligand for that receptor?
Increasing the number of receptors, a process
called up-regulation, makes it more likely that a
ligand will bind to the target cell at a given ligand
concentration, and increases the magnitude of the
response of the target cell to the ligand.

Compare and contrast the signal transduction

cascades initiated by intracellular receptors and Gprotein coupled receptors.
For intracellular receptors: The ligand, which is
hydrophobic, can easily cross the membrane of the
target cell and enter the cytoplasm where it will bind
to its receptor. The binding of the ligand to the

receptor changes the shape and activates the

receptor, which will act as a transcription factor,
promoting gene transcription in the nucleus. By
modifying gene transcription, hydrophobic ligands
that bind to intracellular receptors generally have
slow effects (it may take many hours before cellular
function is modified).
For G-protein coupled receptors: The ligand, which
is hydrophilic, cannot cross the membrane of the
target cell and will instead bind to a receptor on the
external surface of the target cell membrane. The
bind of the ligand to the membrane-bound receptor
will cause a conformation change in the receptor,
leading to the activation of the G-protein,
associated to the receptor on the intracellular side.
The activated or subunits of the G-protein
move through the membrane and activate an
enzymatic amplifier that catalyzes the formation of
a second messenger. A single activated amplifier
enzyme can catalyze the formation of thousands of
molecules of second messenger. Second
messengers then act to modify the function of the
target cell. Because of the amplification process,
and because second messengers typically activate
or inhibit enzymes or membrane channels that are
already present in the target cell, this type of signal
transduction is much faster (cellular function can be
modified in milliseconds).

Compare and contrast the function of heterotrimeric

G proteins and a small soluble G protein such as
Ras.
There are important similarities between them: both
are located on the intracellular side of the
membrane and become activated when a ligand
binds to its associated membrane bound receptor.
Both are bound to GTP when activated, and to GDP
when inactivated.
They differ in how they are involved in signal
transduction: Activated Ras typically activate a
phosphorylation cascade that will lead to the
activation of kinases, while activated G-proteins
split into subunits that activate ion channels (
subunits) or enzymatic amplifiers ( subunit) that
eventually lead to the production of second
messengers.

What is the difference between signaling through

Gs and Gi?
When a ligand binds to a receptor that interacts
with a Gs protein, the s subunit of the Gs will
activate adenylate cyclase, leading to an increase
in the intracellular level of the second messenger
cAMP. When a ligand binds to a receptor that
interacts with a Gi protein, the s subunit of the Gi
will inhibit adenylate cyclase, leading to a reduction
in the production of cAMP. Together, Gs and Gi
signaling pathway regulate the intracellular levels of
cAMP.

What are the major parts of any control system

(mechanical or biological)? Choose an example of
a biological control system and show how it fits the
general description of control systems that you
provided.
Control systems have the following components: A
sensor that detects levels of a regulated variable;
An integrating center (or controller) that evaluates
these levels and determines if they are too low or
too high and sends appropriate signals to effectors
that will change the level of the regulated variable.
A possible example of a biological system would be
how the cells of the pancreas regulate blood
glucose through insulin secretion. Increases in
blood glucose (the regulated variable) are detected
by pancreatic cells (acting as a sensor and
integrating center), which react by secreting insulin
that will cause most cells of the body (the effectors)
to increase glucose uptake, thus decreasing blood
glucose levels.

Compare and contrast positive and negative

feedback. Provide a biological example for each
type of feedback.
For negative feedbacks, effectors cause the
regulated variable to move in the opposite direction
of the initial disturbance, thus keeping the regulated
variable relatively constant around a predetermined
setpoint. For positive feedbacks, effectors cause
the regulated variable to change in the same
direction as the initial disturbance, thus causing the
regulated variable to change very quickly away
from the setpoint.
A possible example of a biological negative
feedback system would be the regulation of body
temperature by the hypothalamus. A decrease in
body temperature below the setpoint is detected by
the hypothalamus, which reacts by triggering neural
signals that will increase heat production (for
example by shivering) and a decrease in heat loss
(for example by peripheral vasoconstriction), which
will cause body temperature to rise back toward the
setpoint.
A possible example of a positive feedback system
would be the role of oxytocin in regulating uterine
contraction during parturition. When parturition
begins, pressure on the cervix stimulates stretch
receptors that send a neural signal to the brain,
which causes pituitary to secrete oxytocin. Oxytocin
binds to receptors on the smooth muscles of the
uterus, causing an increase in uterine contraction.
Uterine contractions cause more pressure on the
cervix, which leads to more oxytocin to be secreted,
and so on until parturition is complete, when
pressure on the cervix is released and the signal
stops.

Compare and contrast the anterior and posterior

pituitary.

For the posterior pituitary, neurons, for which the

cell bodies are located in the hypothalamus and for
which the axon extends into the posterior lobe of
the pituitary, secrete neurohormones in the
circulatory system. Therefore, the posterior pituitary
can be considered an extension of the brain, rather
than an independent organ.
The anterior pituitary is an independent endocrine
organ, but its activity is directly controlled by
neurohormones secreted by the hypothalamus.
Hypothalamic neurons secrete neurohormones in
the hypothalamic-pituitary portal system that carries
these chemical signals to the anterior pituitary. In
response to these chemical signals, the anterior
pituitary secretes hormones into the circulatory
system.

Compare and contrast the insulin/glucagon system

for blood glucose regulation in the vertebrates with
the function and regulation of crustacean
hypoglycemic hormone (CHH).
In vertebrates, two hormones that have antagonist
effects (insulin decreases blood glucose; glucagons
increases blood glucose) work together to keep
blood glucose levels constant. Both insulin and
glucagons are peptide hormones produced by
typical endocrine cells, and bind to transmembrane
receptors of target cells.
The crustacean hyperglycemic hormone (CHH)
could be considered the glucagon equivalent in
these invertebrates. Like glucagons, it is also a
peptide that binds to transmembrane receptors of
target cells and has hyperglycemic effects, but is
secreted by neuron and is therefore considered a
neurohormone. Unlike glucagon, CHH can be
regulated by a positive feedback system. Target
cells can release lactate in response to CHH
stimulation. Lactate can then promote the secretion
of more CHH, which will lead to more lactate
release by target cells, and so on.

Outline the major steps of the vertebrate stress

response.
When dealing with an emergency, animals must
have the resources to escape or confront the threat.
This "fight-or-flight" response begins when the
brain, which evaluates the nature and level of the
threat, detects a stressful stimulus. The brain will
then activate various pathways to deal with the
stressful situation. The somatic nervous system will
be used to stimulate skeletal muscles so that the
animal can fight or run away from the threat.
The sympathetic division of the autonomic nervous
system will be activated. This will directly increase
cardiac output, breathing rate, and redistribute
blood to essential organs. The sympathetic nervous
system will also stimulate the secretion of
catecholamine (epinephrine/norepinephrine) by the
adrenal medulla; these hormones will produce

similar effects as the sympathetic nervous system,

and will also have hyperglycemic effects. The
sympathetic nervous system will also stimulate the
pancreas to increase the rate of glucagons
secretion and to decrease the rate of insulin
secretion. This will also have hyperglycemic effects.
As a result of sympathetic stimulation, physiological
changes will occur that will very quickly insure that
the brain and skeletal muscles receive the oxygen
and fuel they need to deal effectively with the
emergency situation.
In addition to the sympathetic nervous system, the
brain will also trigger responses that will lead to the
activation of the adrenal cortex in response to a
stressful stimulation. The hypothalamus will secrete
CRH in the hypothalamic-pituitary portal system.
CRH will stimulate the secretion of ACTH from the
anterior pituitary into the circulation. ACTH will
promote the release of glucocorticoids, such as
cortisol, by the adrenal cortex. Similar to the effects
of catecholamines, glucocorticoids will lead to an
increase in blood glucose, but this increase will be
much slower because of the relatively slow action
of steroid hormones. Thus, the function of
glucorticoids is more important during the recovery
phase after the emergency occurred.

Epinephrine and glucagon both act to increase

blood glucose, but they act on a different subset of
tissues. What characteristics are likely to determine
whether a particular tissue responds to epinephrine,
glucagon, or to both hormones?
Cells of different tissues often have receptors for
different ligands. Therefore, although most tissues
of the organism may be exposed to both
epinephrine and glucagon, only those tissues for
which the cells have adrenergic receptors will
respond to epinephrine, and only tissues for which
the cells have glucagon receptors will respond to
that hormone.

People who do not regularly drink coffee often feel

much greater effects when they ingest modest
doses of caffeine than do heavy coffee drinkers.
Explain at a molecular level why this might be so.
Caffeine acts as a stimulant by inhibiting receptors
for adenosine, a neurotransmitter that has calming
effects by reducing brain activity. Sustained, chronic
use of caffeine leads to the up-regulation of
adenosine receptors, making the brain more
sensitive to adenosine levels. As a result, regular
coffee drinkers require a higher dose of caffeine
because more adenosine receptors must be
inhibited to achieve the same stimulatory effect.

The anticancer drug tamoxifen binds to the

estrogen receptor. Tamoxifen inhibits the growth of
breast tissue, but promotes growth of uterine
tissues, thus reducing the risk of breast cancer but
potentially increasing the risk of uterine cancer.

Explain how the same chemical messenger could

have opposite effects in two different tissues.
A given chemical message can have vastly different
effects on different target tissues because of
differences in the receptors binding the ligand.
Receptors may have the same ligand-binding
domain while having different functional domains.
As a result, when tamoxifen binds to a certain
receptor, it may inhibit tissue growth, while it may
do the exact opposite effect when binding to
another type of receptor.

What are the advantages of a multistep signal

transduction pathway in cell-to-cell communication?
Having many steps in the transduction pathway
allows multiple opportunities to amplify the signal.

Epinephrine binds to a G-protein-coupled receptor

that signals via Gs. Acetylcholine binds to a Gprotein-coupled receptor that signals via Gi. You
construct a recombinant receptor with the
extracellular domain of the acetylcholine receptor
and the intracellular domain of the epinephrine
receptor, and transfect it into cultured cells. Your
preliminary experiments indicate that the receptor is
processed correctly, and inserted into the plasma
membrane. If you applied acetylcholine to your
transfected cells, what would you expect to happen
to intracellular cAMP levels? What would happen if
you applied epinephrine? Explain your answers.
Acetylcholine would bind to the receptor (because
of the "acetylcholine" extracellular domain) and
activate the Gs signaling pathway (because of the
"epinephrine" intracellular domain), thus causing an
increase in the intracellular level of cAMP. Applying
epinephrine to the cells would do nothing because it
would not bind to a receptor.

In insects, the Malpighian tubules are involved in

the maintenance of ion and water balance. When
the peptide hormone diuretic hormone is applied to
Malpighian tubules isolated form the blood sucking
insect Rhodnius prolixus, the tubule epithelium
begins to secrete fluid at a rate of approximately
5nL/min. The biogenic amine serotonin has similar
effects, causing secretion at a rate of approximately
4 nL/min. When both chemical messengers are
applied together, however, fluid secretion occurs at
a rate of approximately 45 nL/min. Is this an
example of additivity, synergism, or antagonism?
Justify your answer.
This is an example of synergism because the
combined effect of both chemicals is greater than
the sum of each when present individually. If the
effects were additive, we would expect to observe a
secretion rate of around 9nL/min, and if the effects
were antagonistic, we would expect to observe a
secretion rate between zero and 1nL/min.

Compare and contrast hydrophilic and hydrophobic

messengers in terms of the three main steps of
indirect signaling.

Hydrophobic messengers diffuse readily out of

cells, are transported bound to carrier proteins in
the blood, and diffuse readily into target cells.
Hydrophilic messengers are released from the
signaling cell via exocytosis. They travel dissolved
in the blood and bind with membrane receptors on
the target cell to stimulate a response.

Are amines hydrophilic or hydrophobic

messengers? How does this affect their release,
transport, and signaling?
Most amines are hydrophilic messengers (thyroid
hormone is an exception). They are, therefore,
usually released via exocytosis and signal via
membrane receptors.

Why do some cells respond to a chemical

messenger while other cells ignore it?
Cells will only respond to chemical messengers for
which they possess appropriate receptors.

Compare and contrast receptor up-regulation and

down-regulation. How do these phenomena help to
maintain homeostasis?
Cells can up-regulate or down-regulate receptors in
response to regular over-stimulus or over-inhibition.
In this way, the cellular responses to these regular
events can be reduced or increased to homeostatic
levels.

Compare and contrast intracellular and

transmembrane receptors.
Intracellular receptors act as transcription factors
that regulate the transcription of target genes.
Transmembrane receptors interact with the
chemical signal at the cell surface to initiate
responses in the target cell.

Compare and contrast the different types of

membrane receptors and their signal transduction
pathways.
The three types that should be compared here are:
ligand-gated ion channels, receptor enzymes and G
protein coupled receptors. Ligand-gated ion
channels change the ion permeability of the
membrane. Receptor enzymes activate or
inactivate intercellular enzymes. G-protein coupled
receptors activate an associated G-protein that
initiates a signal transduction pathway that causes
a response in the target cell.

What are second messengers and what is their

functional importance? Explain how signal
transduction pathways cause signal amplification.
Select one signal transduction pathway, and outline
specific examples of amplification.
Second messengers are short-lived intracellular
messengers that act as intermediates in signal
transduction pathways. As a single molecule of
activated amplifier enzyme can catalyze the
conversion of thousands of molecules of second
messenger, which can then go on to activate or

inhibit a variety of cellular pathways, pathways that

include second messengers have a greatly
enhanced capacity for signal amplification.

What are the primary functions of endocrine

systems?
The primary function of endocrine systems is to
regulate physiological systems across long
distances. They regulate systems associated with
homeostasis and processes like growth and
reproduction, for which the use of circulating
chemical messengers is more appropriate than
direct cell or neural signaling.

What are antagonistic pairings? What are the

advantages of this organization of control systems?
Antagonistic pairings are systems in which one
hormone increases a particular phenomenon and
the other decreases it. By acting together in this
way, they allow the endocrine system to exert
precise control over the relevant physiological
function.

Compare and contrast negative feedback and

positive feedback. Which type of control allows
maintenance of homeostasis?
Negative feedback is where the product inhibits
further production of the stimulus. Positive feedback
is where the product stimulates further production
of the stimulus. Negative feedback allows
maintenance of homeostasis.

Compare and contrast additivity and synergism.

When two or more hormones increase the
response by an amount equal to the sum of their
separate effects, then their combined effect is
called additive. When in a similar situation the
combined effect is greater than the sum of the
separate effects, it is called synergistic.

Provide an example of a hormone controlled by a

3rd order endocrine pathway, and outline each step
in the regulatory cascade.
Most of the hormones associated with the
Hypothalamic Pituitary Adrenal, HPA, axis (e.g. the
glucocorticoids) or the Hypothalamic Pituitary
Gonadal, HPG, axis (e.g. testosterone, estrogen,
progesterone) are controlled by 3rd order endocrine
pathways.

__________ are specialized protein complexes that

create an aqueous pore between the cytoplasms of
two adjacent cells.
Gap junction

The time taken to reduce the concentration of a

chemical messenger by half is called the
__________.
half life

__________ is the general term for any small

molecule that binds specifically to a protein.

Ligand

Hydrophobic hormones cannot travel in an aqueous

environment for a long distance, so they are usually
bound to (a) __________.
Correct Answers:
carrier protein
albumin
globulins

Chemicals that can mimic that action of a ligand by

activating its receptor are called __________.
agonists

__________ occurs when the number of receptors

on the target cells decrease, in an attempt to
reduce a response.
Down regulation

The DNA-binding domain that an intracellular

receptor binds to to alter transcription rates is
termed __________.
response elements

__________ is a low molecular-weight diffusible

molecule that acts as part of signal transduction
pathways to communicate signals within the cell.
Second messenger

The regulation of blood glucose by insulin is an

example of (a) __________ feedback loop because
the pancreas secretes insulin when it senses an
increase in blood glucose (without involving
integrating centers like the brain).
direct

__________ occurs when the net effect of adding

two different hormones at the same time has a
much greater effect than the sum of the effects
observed when any hormone is injected alone.
Synergism

Direct cell signaling

Can occur through pores called gap junctions.

Autocrine signaling
Can occur when a chemical messenger diffuses
from the signaling cell and binds onto receptors on
the same cell.

Paracrine signaling
Can occur when a chemical messenger diffuses
from the signaling cell and binds to receptors on
nearby cells.

Endocrine signaling
Can occur when a chemical messenger travels a
long distance by entering the circulatory system to
a target cell.

Neural signaling

Electrical signals travel within a single cell and then

either enter the target cell by gap junctions, or
trigger a chemical messenger to be released into a
synapse.

Peptides
Consist of two or more amino acids linked in a
series.

Eicosanoids
A class of lipids that bind to transmembrane
receptors.

___________ are specialized protein complexes

that create an aqueous pore between the
cytoplasms of two adjacent cells.
Gap junctions

How do most hydrophobic chemical messengers

get transported to a target cell?
They bind to carrier proteins in the blood.

When a chemical messenger (or ligand) reaches a

target cell, it binds to a receptor. A hydrophobic
ligand binds to a(n) ________, whereas a
hydrophilic ligand binds to a(n) ___________.
intracellular receptor; transmembrane receptor

The strength of binding between a ligand and a

receptor is usually expressed as the:
affinity constant (Ka)

A transcription factor is a receptor with three

domains: a ligand-binding domain, a DNA-binding
domain, and a transactivation domain. What kind of
receptor is a transcription factor?
Intracellular receptor

Intracellular receptor
When a ligand binds to an ion channel, the channel
changes conformation and the ion channel opens,
allowing ions to cross the membrane.

The signal transduction pathways of _____ involve

phosphorylation cascades.
receptor-enzymes

Three types of receptor-enzymes found in animals

are:
1) receptor guanylate cyclases
2) receptor tyrosine kinases
3) receptor serine/threonine kinases.

A _____ has an extracellular ligand-binding domain,

a transmembrane domain, and an intracellular
catalytic (enzyme) domain.
receptor-enzyme

_____________ rely on ___________, such as

Ca2+, cyclic GMP, phosphatidylinositol, and cyclic
AMP, to activate (or inactivate) a variety of
pathways within the cell.

G-protein-coupled receptors; second messengers

_____ and _____ act as second messenger in two

branches of the phosphatidylinositol signaling
pathway.
Inositol triphosphate (IP3)
diacylglyerol (DAG)

Most Ca2+-mediated signal transduction cascades

act through the protein calmodulin, a Ca2+-binding
protein that is present in _____ cell.
every eukaryotic

The first second messenger to be identified was

_____.
cAMP

Communication among neurons and between

neurons and other target cells occurs across short
distances at a structure called the __________, a
region where the signaling cell and the target cell
are very close together.
synapse

MAP kinases are in the _____ phosphorylation

cascade.
serine/threonine

Norepinephrine, acetylcholine, and serotonin are

what kind of hormones?
Amines.

_____________ are chemicals released by one

animal that cause reactions in another animal of the
same species.
Pheromones

In a ______________, a sense organ senses the

stimulus and sends a signal to the integrating
center (e.g., the brain), which sends out a signal via
a neuron to an endocrine gland. The endocrine
gland releases a hormone into the circulatory
system, which carries the hormone to the target
organs (e.g., heart, lungs, and muscles).
second-order feedback loop

What is ecdysone?
A steroid hormone found only in invertebrates.

In indirect cell communication, a chemical

messenger is _____ from the signaling cell into the
extracellular environment.
released

In indirect cell communication, a chemical

messenger is _____ through the extracellular
environment to the target cell.
transported

In indirect cell communication, communication of

the signal to the target cell happens via _____.
receptor binding


_____ are often synthesized as large inactive
polypeptides and stored before their release.
Peptide hormones

All _____ use a series of related as chemical

messengers, including estrogens androgens, and
glucocorticoids.
vertebrates

Invertebrates have very few endocrine glands, and

most of their endocrine signaling utilizes _____.
neurohormones

The similarities of endocrine systems likely stem

from the evolution of endocrine systems from a
shared set of basic _____ mechanisms involved in
paracrine communication.
signal transduction

The similarities of endocrine systems likely stem

from the evolution of endocrine systems from a
shared set of basic signal transduction mechanisms
involved in _____ communication.
paracrine

_____ and _____ combine to form thyroid

hormones.
MITs
DITs

Lysosomes break down thyroglobulin containing

_____ and _____.
T3
T4

Iodinase adds one or more iodine molecules to

tyrosine molecules of _____.
thyroglobulin

Dopamine, serotonin, thyroid hormone, are all

_____.
biogenic amines

In most physiological situations, direct

communication via gap junctions involves the
movement of _____ between cells.
hydrophilic messengers

Peptide and protein chemical messengers dissolve

well in _____ solutions.
aqueous

A receptor signals changes to the target cell by

changing _____.
shapes

How do carrier proteins work?

Carrier proteins help hydrophobic chemical
messengers dissolve in aqueous solutions by
surrounding the messenger and isolating it from the
solution.

Steroid hormones can easily cross the membrane

of the target cell, and thus they can bind to.....
either transmembrane receptors or intracellular
receptors

A target cell can respond to a _____ only if the

appropriate receptor is expressed on or in the
target cell.
ligand

_____ of hormone receptors results in increased

sensitivity.
Up-regulation

The signal caused by a chemical messenger must

be _____ in order for the body to be able to
respond to changing conditions.
Terminated
4 types of signaling
direct, indirect, endocrine, neural

this type of signaling between cells requires a

connection
direct

this type of signaling includes both paracrine and

autocrine signaling
indirect

this type of signaling utilizes electrical signaling

neural

the protein subunit that composes the gap junction of

cells
connexin

the name of the gap junction for cell signaling

connexon

the name of gap junction for cell signaling in

invertebrates
innexin

the small space where chemical messages diffuse

across from neurotransmitter to receptor
synapse

this cell signal is longer lasting that other types,

involved long lasting hormones and moves through
circulatory system
endocrine

this hormone is secreted into the ducts of external

environment
exocrine

electrical signals travel down this portion of a neuron

axon

pheromones are secreted from the circulatory

system into this type of gland
exocrine

If a hormone is ____ it will be stored in vesicles until

ready to be released via exocytosis
hydrophilic

If a hormone is ___ it will be diffuse, moving through

aqueous solutions and bind to proteins
hydrophobic

This messenger can be both hydrophilic and

hydrophobic, based on r group
amino acids

This messenger is 50 or fewer amino acids,

hydrophilic and cannot diffuse across membrane
peptides

This peptide messenger has 50 or more amino acids

and is hydrophilic
proteins

Of all types of chemical messengers,

neurotransmitters are only composed of ___.
amino acids

This is a inactive protein, which possess a signal

sequence which targets it for secretion from the cell.
The signal sequence in cleaved.
preprohormone

Peptide hormones are synthesized by ribosomes on

the...
rough ER

This peptide hormone is synthesized by ribosomes

on the rough ER.
preprohormones

This is the location where the signal on a

preprohormone is cleaved off.
Rough ER

In the ___, the prohormone is packaged into

secretory vesicles where it is cleaved into an active
hormone and released from the cell.
Golgi

chemical messengers bind to the ..

ligand binding domain

These messengers cannot be stored. They must be

synthesized as needed.
hydrophobic

Gap junctions form by combining ___- ___ innexins

or connexins.
4, 6

Name 2 gas messengers that diffuse freely across

the cell membrane.
nitric oxide, carbon monoxide

Name the 4 components of the signal tranduction

pathway.
receiver, transducer, amplifier, responder

Intracellular pathways use intracellular receptors

which utilize ___ messengers.
hydrophobic

Receptor enzymes are named for...

reactions they catalyze.

G coupled protein receptors have three subunits.

Name them.c
alpha, beta, gamma

These act as second messengers for the G protein

coupled receptors (c, c, p, c)
calcium, cGMP, phosphatidyl inositol, cAMP

This molecule has four binding sites and becomes

activated when filled with calcium
calmodulin

Found in neurons, that secrete neurotransmitters

called catecholamines.
CAM II

When cytoplasmic Calcium increases in neurons,

this concentration activates ___
CAM kinase II

In regulation of cell signlaing, the sensor detects

level of ____
regulated variable

In regulation of cell signaling, this evaluates the

incoming information and sends out a signal to
effector that provokes an appropriate response.
integrating center

This feedback regulates a variable back to a set

points. Most common
negative

This feedback regulates a variable to reinforce and

amplify signals.
positive

feedback regulation at the local level occurs via ___

and ___
paracrine, autocrine

feedback regulation at the long distance level occurs

via ___ and ___
nervous, endocrine

Sense organ sends a signal using the nervous

system to an integrating center. Brain interprets then

transmits via neurotransmitter or neurohormone to a

specific target organ to cause a response.
first order feedback loop

Sense organe detects the level of regulated variable.

Sends a signal to integrating signal which sends a
signal through neuron to endocrine gland, secretes a
hormone. Travels to target cell and initiates a
response.
second order feedback loop

Second order feedback loops are regulated by 2

points
endocrine, sense organe

Endocrine gland secretes hormone and binds to

receptor. In second endocrine gland, hormone
travels through circulatory system to target organ.
third order feedback loop

targeted tissue that causes (effects) a change in the

regulated variable.
effector

In a ___ feedback loop, the effector brings the

varialbe back toward a predtermined set point
negative

In a ___ feedback loop the system responds to a

change in the regulated variable by causing further
deviation from the set point.
positive

___ feedback loops involve only the endocrine

system, and the endocrine gland acts both as the
integrating center and as the tissue that
communicates with the target organ.
direct

a type of cell signaling in which a single cell signals

another cell of the same type, including itself.
autocrine

a signal ofe one type may be changed to another

type of signal using a ___.
transducer

steroid hormones involved in water and ion balance

mineralocorticoids

steroid hormone involved in the stress response that

regulate carbohydrate, protein and lipid metabolism
glucocorticoids
Name six types of cell-to-cell communication in
animals. How do these types vary?
direct, autocrine, paracrine, neural, endocrine,
exocrine
in the distance that the chemcial messengers travel
from one cell to another.

Chemical messengers involved in _____ cell

signaling must travel through both aqueous and lipid
environments. Thus _____ and _____ chemical
messengers face different challenges during cell
signaling.
indirect
hydrophobic
hydrophilic

Chemical messengers involved in indirect cell

signaling must travel through both _____ and _____
environments. Thus hydrophobic and hydrophilic
chemical messengers face different challenges
during cell signaling.
aqueous
lipid

Hydrophilic messengers can travel between adjacent

cells via _____, but more complex mechanisms are
required for indirect cell-to-cell communication
between cells that are not adjacent.
gap junctions

_____ messengers can travel between adjacent

cells via gap junctions, but more complex
mechanisms are required for _____ cell-to-cell
communication between cells that are not adjacent.
Hydrophilic
indirect

Indirect cell signaling involves what three steps? The

mechanisms involved in these steps differ depending
on what?
1) Release of the messenger from the signaling cell.
2) Transport through he extracellular environment.
3) Communication with the target cell.
Whether the the signaling molecules is hydrophobic
or hydrophilic.

_____ messengers are often peptides.

Hydrophilic

Hydrophilic messengers are often _____.

peptides

Hydrophilic messengers are often peptides. They are

released from the signaling cell by _____ and bind to
_____ on the target cell.
exocytosis
transmembrane receptors

Peptide hormones are often synthesized as what?

Where are they processed and when are they
released?
Large preprohormones that are processed within the
signaling cell prior to the release of the active
hormone.

Hydrophobic messengers are synthesized on _____

and _____ out of the signaling cell. _____ proteins
transport them to target cells where they bind to

_____ receptors. Some hydrophobic messengers

also bind to _____ receptors.
demand
diffuse
Carrier
intracellular
transmembrane

_____ messengers are synthesized on demand and

diffuse out of the signaling cell. Carrier proteins
transport them to target cells where they bind to
intracellular receptors. Some _____ messengers
also bind to transmembrane receptors.
Hydrophobic
Hydrophobic

_____ messengers are often steriods.

Hydrophobic

Hydrophobic messengers are often _____.

steriods

_____ are derived from cholesterol.

Steroids

Steroids are derived from _____.

cholesterol

Name the three primary vertebrate steroid

hormones.
minerlocorticoids
glucocorticoids
reproductive hormones

The primary vertebrate ______ are

minerlocorticoids, glucocorticoids, and reproductive
hormones.
steroid hormones

The primary invertebrate _____ are the

ecdysteroids.
steroid hormones

The primary invertebrate steroid hormones are the

_____.
ecdysteroids

Amines can be _____, _____, or _____. These

messengers are derived from hydrophilic _____, and
are often hydrophilic messengers, but the amine
_____ hormones are hydrophobic.
paracrines, hormones, or neurotransmitters
amino acids or peptides
thyroid

The amine thyroid hormones are _____.

hydrophobic

_____ can be paracrines, hormones, or

neurotransmitters. These messengers are derived

from hydrophilic amino acids or peptiedss, and are

often hydrophilic messengers, but the _____ thyroid
hormones are hydrophobic.
Amines
amine

Chemical messengers involved in _____ cell

signaling bind specifically to specific receptor
proteins on or in the target cell. Thus, chemical
messengers act as specific _____ for those
receptors.
indirect
ligands

_____ chemical messengers can interact with

intracellular receptors or transmembrane receptors.
_____ chemical messengers can only interact with
transmembrane receptors.
Hydrophobic
Hydrophilic

Ligand-receptor binding obeys the law of _____, and

exhibits _____. The _____ describes the tightness of
binding between a ligand and a receptor.
mass action
saturation
affinity constant

Ligand-receptor signaling must be _____ for

signaling to be effective.
terminated

Signal termination can be accomplished in a variety

of ways, including.....
Removal of the ligand.
Removal of the receptor from the membrane.
Inhibition of th receptor.
Inhibition of downstream signaling pathways.

Each step in a _____ can amplify the signal.

signal transduction pathway

Each step in a signal transduction pathway can

_____ the signal.
amplify

Signal transduction via _____ channels is relatively

simple and direct, but the other signal transduction
pathways have many steps.
ligand-gated ion

_____ receptors regulate gene transcription.

Intracellular

Intracellular receptors regulate _____.

gene transcription

_____ activate intracellular phosphorylation

cascades.
Receptor-enzymes

Receptor-enzymes activate intracellular _____

cascades.
phosphorylation

G-protein-coupled receptors interact with _____ G

proteins.
heterotrimeric

G proteins can signal to _____ or to _____ that

activate small molecules call second messengers.
ion channels
amplifier enzymes

G proteins can signal to ion channels or to amplifier

enzymes that activate small molecules call _____.
second messengers

G-protein-coupled receptors use what four different

second messengers? Each of these messengers
links to what?
Ca2+, cGMP, inositol phosphates, cAMP
A different signal transduction cascade.

Cells have numerous types of transmembrane and

intracellular receptors, and thus several signal
transduction _____ can be activated at any given
time. Thus, signal transduction _____ in living cells
operate as complex _____ that integrate the various
signals and convert them into appropriate _____.
cascades
cascades
networks
physiological responses

The organization of endocrine systems varies among

animals. Endocrine communication in the _____
generally involved neurohormones, whereas
hormones are more common in _____.
invertebrates
vertebrates

Endocrine systems are responsible for.....

maintaining homeostasis and regulating growth,
development, and reproduction.

_____ systems allow the maintenance of

homeostasis (e.g., control of blood glucose by
insulin).
Negative feedback

_____ allows explosive responses.

Positive feedback

Positive feedback allows _____.

explosive responses

Hormones are often grouped into _____ that allow

extremely precise homeostatic regulation (e.g.,
insulin and glucagon).
antagonistic pairs

Hormones can also work _____ or _____ (e.g.,

glucagon, cortisol, and epinephrine).
additively
synergistically

Hormones can regulate _____ by negative feedback,

in regulatory loops of varying complexity (e.g., the
hormones of the vertebrate anterior pituitary).
other hormones

Name an example of how hormones can regulate

other hormones by negative feedback, in regulatory
loops of varying complexity.
hormones of the vertebrate anterior pituitary

Hormones can also be involved in _____ regulation

(e.g., oxytocin).
positive feedback

Hormones can also be involved in positive feedback

regulation (e.g., _____).
oxytocin

Hormones can also work additively or synergistically

(e.g., _____).
glucagon, cortisol, and epinephrine

Hormones are often grouped into antagonistic pairs

that allow extremely precise homeostatic regulation
(e.g., _____).
insulin and glucagon

Negative feedback systems allow the maintenance

of homeostasis (e.g., _____).
control of blood glucose by insulin

The vertebrate stress response is an example of

what?
Coordination of physiological functions by multiple
signaling systems.

The vertebrate _____ is an example of coordination

of physiological functions by multiple signaling
systems.
stress response
Cell Signaling
1. Production of a signal in one cell (Signaling cell)
2. Transport of that signal (Chemical Messenger) to
a target cell
3. The messenger binds to a receptor to transduce
signal into the target cell

Types of Cell Signaling

-Direct
-Indirect

Direct Signaling
-Gap Junctions
-Connexins

Indirect Signaling

-Autocrine Signaling
-Paracrine Signaling
-Endocrine Signaling
-Neural Signaling

Direct signaling
-Gap junctions or specialized membrane junctions
(tunnels) of adjacent cells.
-Messengers can travel through the tunnel directly
-Without ever leaving the aqueous envelop of the
cell
-Messengers: Ions, small molecules, and water
-Not passive: Opened and Closed to regulate
communication of substances between cells

Indirect Signaling
Other strategies must be used to send signals to
distant cells or to neighboring cells that are not
connected by gap junctions

Steps for Indirect Signaling

1. Release of chemical messenger from signaling
cell into environment
2. Transport of chemical messenger through
environment to target cell
3. Communication of signal to target cell receptor
binding

Autocrine/ Paracrine Signaling

-Messengers move by diffusion
-Distance limit the rate of diffusion
Diffusion is insufficient to carry signals to distant cells

Autocrine Signaling
When the messenger affects signaling cells

Paracrine Signaling
When the messenger affects nearby cells

Endocrine Signaling
-Messenger is secreted (Hormone)
-Travel from signaling cell to the target cell carried by
circulatory system
-Long distance to target cell

Glands
Secretory cells of the exocrine and endocrine tissues
are often grouped into these structures

Nervous (Neural) Signaling

-Electrical signal travels across a long distance
Cell Signaling:
chemical messengers: Receptors: Signal
transduction:

Endocrine signaling
Feedback loops: Pituitary glands: Glucose
metabolism.

Direct Cell signaling

adjoined cells: Send chemical messenger through

gap junction and response occurs

Autocrine & paracrine signaling:

chemical messenger is exported to nearby cell,
binds to receptor: Signal transduction->Response
Para=other cell
Auto=same cell signaling.

Endocrine signaling:
Signaling cell sends chemical messenger into
circulatory system. Leaves circ. syst. & binds to
receptor, signal transduction, response.

Neural Signaling
Neuron: Sends electrical signal: meets end of axon
& releases neurotransmitter:
Binds to receptor, signal transduction, response.

Direct Contact
Gap junctions: connexins: Assemble together to form
pore: electrically connected
Action pot: mov't of charged particles:
ex: cardiac muscle

Indirect signalling:
1.) neighboring cells, not connected by gap junctions
2.) Trans. of chem. mess. to a target cell
3.) Comm. of the signal to the target cell via receptor
binding.
ex: if cell is lacking estrogen receptor & is sent
estrogen, there won't be a cell response

Which cells can participate in autocrine/paracrine

signalling
Almost every cell can participate: always nearby
cells

Nervous signaling:
Electrical & chemical: all the rest are chemical.

What has the greatest signaling distance?

Exocrine signalling has greatest distance.

Exocrine glands:
Release secretions->ducts->body surface
-used for comm., protection, digestion, locomotion.

Endocrine glands:
Release secretions (hormones) direct to circulatory
system.

What type of signaling allows for chemical

messenger diffusion to nearby target cell signalling
transduction pathways?
Paracrine signalling.

Pheromones are examples of

Exocrine secretions.

Hyrdophilic Messengers:
Storage:

Secretion:
Transport:
Receptor:
Effects:
Intracellular vesicles
Exocytosis
Dissolved in extracellular fluids.
Transmembrane
Rapid

Hydrophobic Messengers:
Storage:
Secretion:
Transport:
Receptor:
Effects:
Synthesized on demand
Diffusion across membrane
Short Dist.: Dissolved in extracellular fluid
Long Dist.: Bound to carrier protein
Intracellular or transmembrane.
Slower or Rapid

chemical messengers:
Chem. Struc. is key to how msg. affects how indirect
signalling works
ex: peptides, steroids, amines, lipids, purines &
Gases.

Peptides:
A.A. can be neurotransmitters: move thru
extracellular fluid or circulation.
Golgi processes-> exocytosis
Hydrophobics need to be transported out to have
effect.
ex: cytokines: hydrophilic: receptor must be on
surface.

Binding to transmembrane receptors:

Peptide messengers cannot transverse the
membrane.
-ligand binding induces a conformational in
receptor and activates intracellular signaling
mechanisms.
Lock & key model: may initiate cascade directly.

Steroids:
Mineralocorticoids: Regulate Na uptake:
-Aldosterone
Glutocorticoid: stress hormones: metabolism:
immune regulation
-Synthesized based on demand.
-Cortisol, Cortisone
Reproductive hormones:
-Estrogen, progesterone, testoterone
Steroids need a carrier:
Bind intracellular receptors: transcription factors:
regulates transcription

Biogenic amines:

Hydrophilic: contain NH2 group

catecholines: Dopamine
Histimine
acetylcholine:
(T3&T4): thyroids: derived from tyrosine:
hydrophobic: key roles in metabolism & temp.

Which of the following chemical messengers would

most likely operate via an intercellular receptor:
Testosterone:

Receptors:
Extremely specific: Lock & key, gene families.
Agonist: Bind and activate
Antagonist: Bind but no activation:
2 domains:
-Ligand binding
- Functional

What will yield cell response with a ligand?

Target cells with increase conc. of receptors will yield
response w/ a ligand.

Regulation:
Up-regulation: Increase of cellular component
Down-regulation: decrease in ability to receive
message.
affects how cell response to msg. to make more of
something.

Indirect signalling compare & contrast:

Hydrophilic:
Release:
Transport:
Receptor Binding:
I
I
Rapid effect: stored in vescicles.
Aqueous enviro. Diffuse in extracellular fluids
(Blood=good)
Extracellular (cell surface)

Indirect signalling compare & contrast:

Hydrophobic:
Release:
Transport:
Receptor Binding:
I
I
Slow or Rapid effect: released on demand
Needs active transporter: carrier pro.
Long distance, can diffuse short distance.
Intracellular (inside cell)

Signal transduction overview:

mechanism of move of molc. out-> in cell.
Transducing cell from outside cell to inside, involve

cascades: subA->subB->subC
(gene expression inc/dec)

Signal Transduction: types of receptors:

Ligand-gated ion channel
Receptor-Enzyme
G-protein coupled receptor
-all bound to membrane
Intracellular receptor:
Inside cell

steps 1-3 of signal transduction-intracellular

receptors:
1. hydrophobic ligands pass through cell membrane
2. inside cell, the ligand binds to the ligand-binding
domain of the intracellular receptors:
3. Ligand binding s the shape of receptor:

steps 4-6 of signal transductionintracellular receptors

4. Receptor-ligand complex translocates to the
nucleus.
5. DNA- binding domain of the receptor binds to
responsive element DNA sequences, and the
transactivating domain interacts with other
transcription factors bound in this region.
6. together, these transcription factors alter the rate
of transcription of the target genes into mRNA.

Ligand-gated ion channels

Induces a conformational in the receptor allowing
specific ions to pass.
-based on electrochemical gradient
- in membrane potential are the signal.

Receptor-Enzymes
Enzyme: bio catalyst.
Induce phosphorylation cascades:
-amp. of signal.
3 classes:
-Receptor guanylate cyclases,
-Receptor tyrosine kinases,
-Receptor serine/thr kinases.

Receptor Guanylate cyclases:

Conf. :
Takes GTP-> cyclic form: Kinases phosphorylate
other enzymes/proteins:
ex: atrial natriuretic peptide receptors
-Blood pressure sensors

Receptor Tyrosine Kinases:

Activate Ras Protein
Bind to receptor: Dimerize: Autophosphorylation
event.
When active, can activate GTP shuttle: on-off switch.
RAS->nucleus
Activate MAPK pathways.

Ras in cancer

Ras is a g protein
Important in signal transduction cascades
Binds GDP/GTP
Ras is a protoncogene
Members of the Ras gene family are mutated in 40%
of tumors
-Mutation locks Ras into an on position, stim. cell
division.

Receptor Serine/Threonine Kinases:

Reactivate OH groups, Directly activate
phosphorylation cascades.
-no Ras needed.

G protein coupled receptors & Ion Channels:

The beta gamma subunit can target ion channels,
causing them to open.
Ca2+ channels:
Influx of Ca2+
Initiates signaling cascade via calmodulin:
Vast downstream targets
Signaling in neurons that results in catecholamine
release.

Dimerization and autophorylation is a characteristic

of the mechanism of activation of:
Receptor Tyrosine Kinases
What are the four indirect cell signaling types? How
long does each last?
Autocrine and paracrine signaling
- Milliseconds to seconds
Nervous signaling
- Milliseconds
Endocrine Signaling
- Seconds to minutes
- Longer-lived
Exocrine Signaling

A nervous signal requires what four things?

Electrical signal
Neurotransmitter
Synapse
Neurohormone

Name the six classes of chemical messengers.

Peptide messengers
Steroid messengers
Biogenic amine messengers
Lipid messengers
Purine messengers
Gas messengers

Name the three peptide messengers and their

hydrophobicity.
Amino acids
- Hydrophilic and hydrophobic
Peptides
- Hydrophilic

 Proteins
- Hydrophilic

What are the three domains of a peptide

transmembrane receptor?
Ligand-binding domain
Transmembrane domain
Intracellular domain

What is the hydrophobicity of steroid messengers?

What is required as they travel extracellularly?
Hydrophobic
Carrier protein

Name two examples of gas messengers, how they

are released from the cell, and how long they last.
Examples:
- Carbon monoxide, nitric oxide
Freely diffuse across the cell membrane
Very short-live

Discuss receptor isoforms.

Many receptors are part of large gene families.
These genes are transcribed into similar proteins,
termed isoforms, with distinct properties. Receptor
isoforms often share similar ligand-binding
domains, but differ in their functional domains. The
presence of these isoforms allows the same
signaling molecule to have very different effects on
different target cells.

Name three things from lecture that are associated

with receptor-ligand interactions.
Ligand must be expressed
Ligand binding domain
Receptor isoform

Name the two types of cell signaling regulation.

What are the three components of these systems?
Negative feedback
Positive feedback
Sensor
- Detects regulated variable
Integrating center
Effector

What types of feedback regulation takes place at

the local level? Long distance?
Local level
- Paracrine signals
- Autocrine signals
Long distance
- Nervous system
- Endocrine system

Name the four subcategories of feedback loops.

Describe each.
Direct: Involves only the endocrine system. The
endocrine gland acts both as the integrating center
and as the tissue that communicates with the target
organ.

First order: Has one step (a neuron that releases a

neurotransmitter or a neurohormone) between the
integrating center and the target organ.
Second order: Has two steps (a neuron and an
endocrine gland) between the integrating center
and the target organ.
Third order: Contains an additional endocrine gland
in the pathway, providing a third point of feedback
regulation.

What are the four components of a signal

transduction pathway?
Receiver
Transducer
Amplifier
Responder

What are the four types of signal transduction

pathways?
Intracellular pathways
Ligand-gated ion channels
Receptor-enzymes
G-protein-coupled receptors

What are the three domains of intracellular

receptors?
Ligand-binding domain
DNA-binding domain
Transactivational domain

What are the three subunits of G-coupled-protein

receptors?
alpha, beta, gamma

What are the four second messengers used by Gprotein-coupled receptors? What enzyme
synthesizes each? What is their action and effects?
Calcium: No enzyme. Binds to calmodulin. Alters
enzyme activity.
Cyclic guanosine monophosphate (cGMP):
Guanylate cyclase. Activates protein kinases
(usually protein kinase G). Phosphorylates proteins
and opens and closes ion channels.
Phosphatidyl inositol: Phopholipase C. Activates
protein kinase C and stimulates Ca2+ release from
intracellular stores. Alters enzyme activity and
phosphorylates proteins.
Cyclic adenosine monophosphate (cAMP):
Adenylate cyclase. Activates protein kinases
(usually protein kinase A). Phophorylates proteins
and opens and closes ion channels.

Describe how calcium channels work. How does

one component benefits us and where is it found?
Calcium channels open
Activation of calmodulin
Ca2++-calmodulin-dependent protein
kinases (CaM kinases) (high in neurons that
secrete the catecholamine neurotransmitters)
- Learning and memory

Discuss cGMP.

 Guanylate cyclase
- Amplifier enzyme
- Activates protein kinase G
Phosphodiesterase
- Amplifier enzyme
- Converts cGMP to GMP
- Closes Na+ channels

Discuss the phosphatidyl inositol pathway.

Phospholipase C
Amplifier enzyme
Products produced:
-Inositol triphosphate (IP3)
-Diacylglycerol (DAG)

sensor (in feedback loops)

Detects regulated variable.

What are steroid messengers derived from? Name

the three main types of steroid hormones and give
an example of each.
Derived from cholesterol
Mineralocorticoids
- Aldosterone
Glucocorticoids
- Cortisol
Reproductive hormones
- Estrogens

Name the class of lipid that can act as a

messenger. What types of messengers can they
be? How long do they last? Give two examples of
lipid messengers from lecture.
Eicosanoids
- paracrine, neurotransmitter
- Very short half-life
- Ex: Prostoglandins
- Ex: Leukotrienes

A ligand is a small molecule that binds specifically

to a larger macromolecule such as a receptor,
causing a response in the target cell. Both _____
and _____ can bind to a receptor, but only _____
cause a response.
agonists
antagonists
agonists

Describe the six steps in signal transduction by

intracellular receptors.
1) Hydrophobic ligands pass through the cell
membrane.
2) Inside the cell, the ligand binds to the ligandbinding domain o the intracellular receptors.
3) Ligand binding changes the shape of the
receptor.
4) The receptor-ligand complex translocates to the
nucleus.
5) The DNA-binding domain of the receptor binds to
responsive element DNA sequences, and the
transactivating domain interacts with other
transcription factors bound in this region.

6)Together, these transcription factors alter the rate

of transcription of the target genes into mRNA.

Describe the structure and function of ligand-gated

ion channels.
When the ligand is bound the receptor, the ion
channel is closed and ions cannot cross the
membrane. When a ligand binds to the ion channel,
the channel changes conformation and the ion
channel opens, allowing ions to cross the
membrane. The resulting change in membrane
potential acts as a signal within the target cell.

Receptor guanylate-cyclases convert ___ to ___.

Receptor tyrosine kinases do what?
Receptor serine/threonine kinases do what?
GTP, cGMP
Receptor tyrosine kinases phosphorylate tyrosine
residues in proteins.
Receptor serine/threonine kinases phosphorylate
serine or threonine resides in proteins.

Describe the five steps in signal transduction via

receptor tyrosine kinases.
1) Ligand binds to receptor.
2) Receptors dimerize and autophosphorylate.
3. Phosphorylated receptors interact with protein
kinases.
4) Protein kinases signal to Ras protein.
5 Ras switches between the active and inactive
forms.

Receptor tyrosine kinases signal through _____

proteins.
Ras

Receptor serine/threonine kinases _____ activate

phosphorylation cascades.
directly (no Ras)

Describe the three steps in receptor

serine/threonine kinase signal transduction.
1) Ligand binds to a receptor serine/thronine
kinase, changing its conformation.
2)The conformational change activates the
serine/threonine kinase domain of the receptor.
3) The serine/threonine kinase phosphorylates
proteins on serine or threonine residues.

Describe the 5 steps in receptor G-protein-coupled

receptor signal transduction.
1) Ligand binds to a G-protein-coupled receptor,
causing a conformational change.
2) The activated receptor signals to an associated
G- protein, causing the alpha subunit to release
GDP and bind GTP.
3) The activated alpha or beta/gamma subunits
move through the membrane and interacts with an
amplifier enzyme.
4) The activated amplifier enzyme converts an
inactive second messenger into its active form.

5) The activated second messenger activates or

inhibits cellular pathways.

One target protein of calmodulin is a diverse family

of _____ kinases called Ca2+-calmodulindependent protein kinases (CaM kinases). One of
the best-studied examples of CaM kinase is _____,
which is found in high concentrations in neurons
that secrete neurotransmitters called
catecholamines. When cytoplasmic Ca2+ increases
in these neurons, the change in Ca2+ concentration
activates _____. _____ phosphorylates tyrosine
hydroxylase (one of the key enzymes in
catechomaimine biosynthesis).
serine/threonine
CaM kinase II
CaM kinase II
CaM kinase II

Describe the ten steps in the inositol-phospholipid

signaling pathway.
1) Ligand binds to a G-protein-coupled receptor,
causing a conformational change.
2) The alpha subunit of the G protein releases GDP
and binds GTP and moves through the membrane.
3) The activated alpha subunit activates
phospholipase C, which cleaves PIP2 into IP3 and
DAG.
4) DAG is cleaved in the membrane to form
arachidonic acid, the substrate for the synthesis of
chemical messengers called eicosanoids.
5) IP3 is released into the cytoplasm.
6) IP3 can be phosphorylated to IP4, which has
diverse effects.
7) IP3 also binds to Ca2+ channels on the
endoplasmic reticulum, releasing Ca2+ into the
cytoplasm.
8) The Ca2+ binds to calmodulin, causing diverse
effects within the cell.
9) The Ca2+ also stimulates protein kinase C
(PKC ) to move to the membrane where it interacts
with DAG.
10) DA activates the PKC, which then
phosphorylates proteins, stimulating a
phosphorylation cascade.

G-protein-coupled signal transduction through

adenylate cyclase can be either _____ or _____.

stimulatory
inhibitory

Describe the seven steps in G-protein signal

transduction via adenlyate cyclase. sigdnaling
pathway.
1) Ligand binds to Gs-protein-coupled receptor,
causing a conformational change.
2) The alpha s subuint releases GDP, binds GTP,
moves through the membrane, and activates
adenylate cyclase.
3) Activated adenylate cyclase catalyzes the
conversion of ATP to cAMP.
4) cAMP binds to the regulatory subunit of protein
kinase A (PKA), which dissociates from the catalytic
subunit activating it.
5) The activated catalytic subunit phosphorylates
proteins, causing a response.
6) The phosphorylated proteins are rapidly
dephosphorylated by serine/threonine
phosphatases, terminating the response.
7) When ligand binds to a Gi-protein-coupled
receptor, the alphai subunit inhibits adenylate
cyclase, inhibiting the signal transduction pathway.

direct feedback loops

Involve only the endocrine system, and the
endocrine gland acts both as the integrating center
and as the tissue that communicates with the target
organ.

first-order feedback loops

Have one step (a neuron that releases a
neurotransmitter or a neurohormone) between the
integrating center and the target organ.

second-order feedback loops

Have two steps ( a neuron and an endocrine gland)
between the integrating center and the target
organ.

third-order feedback loops

Contain an additional endocrine gland in the
pathway, providing a third point of feedback
regulation.