SIXTH SEMESTER !!
Course Title: AUTONOMIC AND SYSTEMIC PHARMACOLOGY
Course Code: VPT-322
Drug acting on autonomic nervous system Lecture-1
Introduction to the autonomic
nervous
system, neurohumoral transmission
Dr. Jibachha Sah
M.V.Sc ( Veterinary Pharmacology)
College of veterinary science, NPI
Bhojard, Chitwan
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Introduction
●The autonomic nervous system (ANS) is that portion of the nervous system that controls the
so-called visceral functions of the body (cardiac function, blood pressure, respiration, glandular
activity, etc.).
The animal nervous system can be divided into
●the central nervous system(CNS), consisting of the brain and spinal cord
● the peripheral nervous system(PNS), consisting of the cranial and spinal nerves
and their branches.
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Four types of nerve fibers are found in most nerves:
(i) somatic afferent (sensory) fibers, which convey impulses
from the head, body wall, and extremities to the CNS
(ii) somatic efferent (motor) fibers, which convey impulses
from the CNS to the striated ("voluntary") muscles
(iii) visceral afferent (sensory) fibers, which convey impulses
from the internal; organs to the CNS
(iv) visceral efferent (motor) fibers, which convey impulses
from the CNS to the internal organs, glands, and the smooth and
cardiac ("involuntary") muscles
Nervous system
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There are two main divisions in the peripheral nervous system
(i) the afferent division and
(ii) the efferent division.
Afferent neurons are sensory neurons that carry nerve impulses from sensory stimuli
towards the central nervous system and brain, while efferent neurons are motor neurons
that carry neural impulses away from the central nervous system and towards muscles to
cause movement.
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A sensory nerve, also called an afferent nerve, is a nerve that carries sensory information
toward the central nervous system (CNS). It is a cable-like bundle of the afferent nervefibers
coming from sensory receptors in the peripheral nervous system (PNS).
A motor nerve is a nerve located in the central nervous system (CNS), usually the spinal
cord, that sends motor signals from the CNS to the muscles of the body.
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Anatomical differences between sympathetic and parasympathetic divisions of
the ANS:
Sympathetic division Parasympathetic division
Origin of preganglionic Spinal nerves T1-L2 Cranial nerves III, VII, IX, X;
fibers (thoracolumbar) spinal nerves S2-S4
Location of ganglia Close to spinal cord. Thus, In or near effector organs;
preganglionic fibers are thus preganglionic fibers
shorter than postganglionic are usually longer than
fibers postganglionic fibers
Branching of preganglionic Extensive branching Limited branching
fibers
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Division of autonomic nervous system
The two divisions of the autonomic nervous system are the sympathetic division and
the parasympathetic division.
The sympathetic system is associated with the fight-or-flight response, and
parasympathetic activity is referred to by the epithet of rest and digest.
For example, the heart receives connections from both the sympathetic and
parasympathetic divisions. One causes heart rate to increase, whereas the other causes
heart rate to decrease.
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Different between sympathetic and parasympathetic ANS
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●Sympathetic – most release norepinephrine (adrenergic).
● Parasympathetic – release acetylcholine .
Acethylcholine (ACh) and Norepinephrine( NE) are the major neurotransmitters in autonomic
nervous system
Acetylcholine
● ALL parasympathetic postganglionic neurons
● ALL preganglionic neurons
● Blood vessels of muscle and sweat gland.
● ACH is rapidly hydrolyzed by a membrane-associated Acetylcholinesterase in the
synaptic cleft.
● Effects are short and localized.
Norepinephrine (Noradrenalin):
● Most sympathetic postganglionic neurons
● Exceptions: Sweat glands (Acetylcholine), Renal arteries (Dopamine).
● Epinephrine (Adrenaline): – Adrenal medulla upon sympathetic impulses
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Chemical Signaling in the Autonomic Nervous System
Where an autonomic neuron connects with a target, there is a synapse. The electrical signal
of the action potential causes the release of a signaling molecule, which will bind to receptor
proteins on the target cell. Synapses of the autonomic system are classified as
either cholinergic, meaning that acetylcholine (ACh) is released, or adrenergic, meaning
that norepinephrine is released.
The cholinergic system includes two classes of receptor: the nicotinic receptor and
the muscarinic receptor. Both receptor types bind to ACh and cause changes in the
target cell.
The nicotinic receptor is a ligand-gated cation channel and the muscarinic receptor is a G
protein–coupled receptor.
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Example:
Imagine two locks—one for a classroom and the other for an office—that are opened by
two separate keys. The classroom key will not open the office door and the office key will
not open the classroom door. This is similar to the specificity of nicotine and muscarine for
their receptors.
However, a master key can open multiple locks, such as a master key for the Pharmacology
Department that opens both the classroom and the office doors. This is similar to ACh that
binds to both types of receptors.
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The adrenergic system also has two types of receptors, named the alpha (α)-adrenergic
receptor and beta (β)-adrenergic receptor. Unlike cholinergic receptors, these receptor
types are not classified by which drugs can bind to them. All of them are G protein–coupled
receptors. There are three types of α-adrenergic receptors, termed α1, α2, and α3, and there
are two types of β-adrenergic receptors, termed β1 and β2.
An additional aspect of the adrenergic system is that there is a second signaling molecule
called epinephrine.
The chemical difference between norepinephrine and epinephrine is the addition of a
methyl group (CH3) in epinephrine.
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Autonomic System Signaling Molecules (Table 1)
Sympathetic Parasympathetic
Acetylcholine → nicotinic Acetylcholine → nicotinic
Preganglionic
receptor receptor
Norepinephrine → α- or β-
adrenergic receptors
Acetylcholine →
muscarinic receptor
Postganglionic
(associated with sweat
glands and the blood
vessels associated with
skeletal muscles only
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Fight or Flight?
The original usage of the epithet “fight or flight” comes from a scientist named Walter
Cannon who worked at Harvard in 1915.
Cannon expanded the idea, and introduced the idea that an animal responds to a
threat by preparing to stand and fight or run away.
Endogenous: describes substance made in the human body
Exogenous: describes substance made outside of the human body
G protein–coupled receptor: membrane protein complex that consists of a receptor protein that binds to a
signaling molecule—a G protein—that is activated by that binding and in turn activates an effector protein
(enzyme) that creates a second-messenger molecule in the cytoplasm of the target cell
Ligand-gated cation channel: ion channel, such as the nicotinic receptor, that is specific to positively
charged ions and opens when a molecule such as a neurotransmitter binds to it
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Receptors
Cholinergic Receptors
● Receptor for Ach.
● classified as nicotinic, muscarinic.
Nicotinic (N) receptors
● All ganglionic neurons of both sympathetic and parasympathetic
● At the neuromuscular junction
● The hormone-producing cells of the adrenal medulla
● The effect of ACh binding to nicotinic receptors is always stimulatory
● named after activation by Nicotine.
Muscarinic (M): at the target organ named after activation by Muscarine (poison of Amanita
muscaria)
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Adrenergic receptors: respond to norepinephrine/epinephrine
●Subdivided in to α and β.
α Adrenergic receptors
●α receptors are located postsynaptically at sympathetic neuroeffector
junctions of many organs.
● In general, alpha receptors mediate excitation or increased activity of the
effector cells.
● Vascular smooth muscle is an important site of alpha receptors.
They are subdivided into two types
1. Located in the vascular smooth muscle of the skin and splanchnic regions,
the gastro intestinal(GI) and bladder sphincters, and the radial muscle of the iris.
● Produce excitation( e. g. contraction or constriction).
2. Are located in presynaptic nerve terminals, platelets, fat cells and
pancreatic islets.
● Effects platelet aggregation
● Vasoconstriction
● inhibition of norepinephrine release and of insulin secretion.
● Often produce inhibition ( e. g. relaxation or dilation). 22
β adrenergic receptors
●are also located postsynaptically at sympathetic neuroeffector junctions of
many organs.
● In general, beta receptors mediate relaxation or Decreased activity of the
effector cells. Thus, Blood vessels dilate and Uterine smooth muscle relaxes in response
to activation of beta receptors.
There are three known types of beta receptor, designated β1, β2 and β3.
(i) β1-Adrenergic receptors : are located mainly in the heart.
● Produce excitation ( e. g. increased HR, increased conduction velocity,
increased contractility).
(ii) β2-Adrenergic receptors: are located on the vascular smooth muscle of skeletal
muscle, bronchial smooth muscle, and in the wall of GI tracts and bladder.
● Produce relaxation( e.g. dilation of vascular smooth muscle, dilation of
bronchioles, relaxation of the bladder wall.
(iii) β3- adrenergic Receptors are located in fat cells.
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Neurohumoral Transmission (NHT)
Neurohumoral transmission refers to the transmission of impulse through synapse and
neuro-effector junction by the release of humoral (chemical) substances.
The term ‘conduction’ stands for the passage of an impulse along an axon or muscle
fibre.
The principal neurotransmitters released from the postganglionic sympathetic and
parasympathetic nerve endings respectively are noradrenaline (NA or norepinephrine,
NE) and acetylcholine (ACh), whereas the transmitter released in ganglia from the
preganglionic nerve ending of both systems is acetylcholine.
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There are a number of other neurotransmitters, which are called as non-adrenergic non-
cholinergic (NANC) transmitters, released from the specific nerve endings. Those include
nitric oxide, serotonin (5-HT), ATP, dopamine, GABA, purines, peptides etc.
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Physiological Steps Involved In NHT:
Axonal Conduction:
●A message or impulse is nothing but the state of depolarization which is
propagated through the nerve fibres for transmission of information through it.
●In normal resting state, a nerve cell is approximately -70 mV negative inside to the
outside.
●Tetrodotoxin (It blocks sodium channels, which carry messages between the brain
and our muscles. As a result, those suffering from tetrodotoxin poisoning initially
lose sensation, Its usual route of toxicity is via the ingestion of contaminated puffer
fish which are a culinary delicacy, especially in Japan) and saxitoxin(a neurotoxin
naturally produced by certain species of marine dinoflagellates and freshwater
cyanobacteria)selectively prevent the increase in permeability to Na+ and thus block
axonal conduction and produces flaccid type of paralysis.
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● Batrachotoxin ( is an extremely potent cardiotoxic and neurotoxic steroidal alkaloid found
in certain species of beetles, birds, and frogs) and Scorpion toxins (Their toxic effect may be
mammal- or insect-specific and acts by binding to sodium channels, inhibiting the
inactivation of activated channels and blocking neuronal transmission), selectively increase
Na+ permeability to cause persistant depolarization which results in spastic paralysis. Local
anaesthetics interfere with the Na+ permeability and block axonal conduction.
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Transmission through Ganglia and Neuro-effector Junctions:
The depolarization of the area leads to stimulation and opening of the voltage sensitive
Ca+ channels of axonal membrane. Ca+ enters into the axoplasm and helps in fusion
between the axoplasmic membrane and synaptic vesicles which are the store houses of
neurotransmitters (excitatory or inhibitory) enzymes and some other proteins. The contents
of those vesicles are then extruded out to the junctional cleft by a process called exocytosis.
This neurally mediated release can be modulated by the transmitter itself or by other
agents through interaction with the pre-junctional membrane receptors. Norepinehrine
(NE, through α2adrenoceptors), dopamine, acetylcholine (through M2 receptors),
adenosine, enkephalins and prostaglandins inhibit NE release.
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Receptor events on post-junctional membrane:
The released transmitters rapidly migrate across the cleft and bind with specific receptors
on the post junctional neuronal or effector cell membrane .
The excitatory neurotransmitters bind with their receptors resulting in increase in
Na+ permeability which causes depolarization followed by K+ efflux or repolarization.
Fate of Neurotransmitters:
The released ACh is rapidly hydrolyzed by acetyl-cholinesterase (AChE) enzyme that
normally localizes in the synaptic cleft.
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Neurohumoral transmission:
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The first set, called preganglionic neurons, originates in the brainstem or the spinal cord, and
the second set, called ganglion cells or postganglionic neurons, lies outside the central
nervous system in collections of nerve cells called autonomic ganglia.
The neuron arising directly from the CNS is called the Preganglionic neuron i.e. the neuron
before the ganglion.
It is important to know that a ganglion refers to a bundle of nerve cell bodies outside of the
CNS. The ganglion gives rise to the second neuron.
The neuron with which the preganglionic neuron synapses ( and which ultimately supplies the
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tissues ) is called Postganglionic neuron.
