INTRODUCTION TO THE

NERVOUS SYSTEM
Uyaiabasi G. Noblefather
DEPT. OF PHARMACOLOGY
BENJAMIN S. CARSON (SNR)
SCHOOL OF MEDICINE
BABCOCK UNIVERSITY
 Objectives
At the end of the lecture, you will be able to do the
following:
 Briefly describe the functions of the sympathetic
nervous system.
 Describe how the autonomic nervous system differs anatomically
from the rest of the nervous system.
 Describe the various division of the ANS
 Identify the effects and function of sympathetic and parasympathetic
stimulations
 Differentiate between sympathetic and parasympathetic stimulations
 Discuss the usefulness of the ANS to humans
• Exodus 4:2-4 And the LORD
said unto him, What is that in
thine hand? And he said, A rod.
3: And he said, Cast it on the
ground. And he cast it on the
ground, and it became a
serpent; and Moses fled from
before it.
4: And the LORD said unto Moses,
Put forth thine hand, and take it
by the tail. And he put forth his
hand, and caught it, and it became
a rod in his hand:
 Nervous System Cont’d
• The nervous system is divided into two anatomical divisions: the
central nervous system (CNS) and the peripheral nervous system
(PNS).

• The CNS is composed of the brain and spinal cord.

• The peripheral nervous system is subdivided into the efferent and

afferent divisions. The efferent neurons carry signals away from the
brain and spinal cord to the peripheral tissues, and the afferent
neurons bring information from the periphery to the CNS.
Nervous System Cont’d
Nervous System Cont’d
Nervous System Cont’d
 Introduction to the Nervous System
• The efferent portion of the peripheral nervous system is further divided
into two major functional subdivisions: the somatic and the autonomic
nervous system (ANS).
• Somatic Nervous System

• The somatic efferent neurons are involved in the voluntary control of

functions such as contraction of the skeletal muscles essential for
locomotion.
• The efferent somatic nervous system differs from the ANS in that a
single myelinated motor neuron, originating in the CNS, travels directly
to skeletal muscle without the mediation of ganglia.
• Responses in the somatic division are generally faster than those in the
ANS.
Nervous System Cont’d

β3

Fig. 1: Organization of the nervous system

 Autonomic Nervous System Cont’d
• The Autonomic Nervous System
• The autonomic nervous system (ANS) is sometimes called the
involuntary or visceral or vegetative. The system is involuntary in nature
and the activities of this system are maintained autonomically. The
control the internal environment of the body.

• The “autonomic” processes never stop attending to the wide range of

metabolic, cardiopulmonary, and other visceral requirements of our
body.

• Autonomic control continues whether we are awake and attentive,

preoccupied with other activities, or asleep .
 Autonomic Nervous System Cont’d
• The system mostly functions with the person having little conscious
awareness of its activity. Working closely with the endocrine system,
the ANS helps to regulate and integrate the body’s internal functions
within a relatively narrow range of normal, on a minute-to-minute
basis.

• While we are awake, we are unaware of most visceral sensory input,

and we avoid any conscious effort to act on it unless it induces distress.

• In most cases, we have no awareness of motor commands to the

viscera, and most individuals can exert voluntary control over motor
output to the viscera only in minor ways.
 Autonomic Nervous System Cont’d
• The ANS is largely outside the influence of voluntary control. It is
composed of efferent neurons that innervate smooth and control the
following processes:
• The autonomic motor neurons innervate smooth muscle, cardiac
muscle, secretory epithelia, and glands .

 contraction and relaxation of vascular and visceral smooth muscle

 all exocrine and certain endocrine secretions

 the heartbeat

 energy metabolism, particularly in liver and skeletal muscle.

 Autonomic Nervous System Cont’d
• ANS is divided into three main divisions.
• Sympathetic
• Parasympathetic
• Enteric nervous system.

• The ANS does not send impulses directly to the periphery. Instead,
axons from CNS neurons end in ganglia, or groups of nerve bodies
that are packed together, located outside of the CNS.
 Autonomic Nervous System Cont’d
• These ganglia receive information from the preganglionic neuron that
started in the CNS and relay that information along postganglionic
neurons.

• The postganglionic neurons transmit impulses to the neuroeffector

cells—muscles, glands, and organs.
• The sympathetic and parasympathetic branches differ in three basic
ways:
• (1) the location of the originating cells in the CNS,
• (2) the location of the nerve ganglia, and
• (3) the preganglionic and postganglionic neurons.
 Anatomy Nervous System

Fig. 2: The Efferent pathway of the ANS

 Anatomy Nervous System Cont’d
• The Sympathetic neurons have short preganglionic neurons and long
post ganglionic neurons. In most cases, the preganglionic nerve
endings of the sympathetic nervous system are highly branched,
enabling one preganglionic neuron to interact with many
postganglionic neurons and activate many effector organs at the same
time.

• The parasympathetic system has long preganglionic fibers and short

postganglionic ones, with the ganglia close to or within the organ
innervated. In most instances, there is a one-to-one connection
between the preganglionic and postganglionic neurons, enabling
discrete response of this system.
 Anatomy Nervous System Cont’d

Fig. 3:Receptors In the autonomic nervous system:(a) sympathetic divison

(b) parasympathetic division
 Neurotransmitters in Nervous System
• Acetylcholine (ACh) is the principal Neurotransmitter (NT) at
Nueromuscular jucmtion as well at all preganglionic fibres.
• In parasympathetic system, NT released at postganglionic fibres is
also ACh.

• In sympathetic system, at most of the postganglionic fibres, NT

secreted is noradrenaline (NA)

• but it can be dopamine (renal and mesenteric vasculature),

• ACh (sweat glands; sympathetic cholinergic) or

• adrenaline (adrenal medulla).

 Neurotransmitter Regulation
• Impulse is conducted along the axon till it reaches the cell body
forming the synapse.

• Cell body releases the NT that acts on the receptors present on the
post-synaptic membrane (post-synaptic receptors) as well as on the
pre-synaptic membrane (pre-synaptic receptors).

• Pre-synaptic receptors increase (nicotinic, β) or decrease (muscarinic,

α2) the release of neurotransmitter from their own neuron
(autoreceptors) or from adjoining neurons (heteroreceptors).
 Organization of Nervous System

Fig. 4: Autonomic system pathways (acetylcholine; D, dopamine; Epi, epinephrine; M, muscarinic receptors; N, nicotinic
receptors; NE, norepinephrine. Coutesy Basic & Clinical Pharmacology 12ed)
 Physiology Nervous System
• Functions of the Autonomic nervous system
• In everyday life, the autonomic nervous system functions
continuously to control specific local functions, such as adjustments
to postural changes, exercise or ambient temperature.

• The sympathetic and parasympathetic mediate the 'rest and digest'

state (parasympathetic active, sympathetic quiescent) to the extreme
emergency fight or flight state (sympathetic active, parasympathetic
quiescent).
 Functions of the Autonomic nervous system
• In some places (e.g. in the visceral smooth muscle of the gut and
bladder, and in the heart), the sympathetic and the parasympathetic
systems produce opposite effects, but there are others where only
one division of the autonomic system operates. For example

• The sweat glands and most blood vessels, for example, have only a
sympathetic innervation.

• The ciliary muscle of the eye has only a parasympathetic innervation.

 Functions of the Autonomic nervous system
• Bronchial smooth muscle has only a parasympathetic (constrictor)
innervation (although its tone is highly sensitive to circulating
adrenaline-acting probably to inhibit the constrictor innervation
rather than on the smooth muscle directly).

• Resistance arteries have a sympathetic vasoconstrictor innervation

but no parasympathetic innervation; instead the constrictor tone is
opposed by a background release of nitric oxide from the endothelial
cells.
 Functions of the Autonomic nervous system
• Effects of stimulation of the sympathetic nervous system: The
sympathetic transmission system is also known as the Noradrenergic
transmission is restricted to and conducted mainly by 3 closely
related catecholamines

• Noradrenaline/norepinephrine – sympathetic post ganglionic nerve

fibre except sweat glands, hair follicle, blood vessels, certain area of
brain.

• Adrenaline/epinephrine – adrenal medulla, chromaffin cells.

 Functions of the Autonomic nervous system
• Dopamine – basal ganglia, limbic system, chemoreceptor trigger zone
(CTZ), anterior pituitary in CNS.

• They prepare the body for emergency situations by direct activation

of effector organs and stimulation of adrenal medulla to release
adrenalin (with little noradrenalin) to prepare the body for the “fight
or flight” response.
 Functions of the Autonomic nervous system
• Effects of stimulation of the parasympathetic nervous system: The
parasympathetic division also known as cholinergic transmission and
ACh is the main neurotransmission.

• Acetylcholine is the NT at most parasympathetic neuroeffector

junction, autonomic ganglia, the adrenal medulla, somatic myoneural
junctions & certain CNS regions.
 Functions of the Autonomic nervous system
• It is involved with maintaining homeostasis within the body, it
maintains essential bodily functions, such as digestion and
elimination of wastes and usually acts to oppose or balance the
actions of the sympathetic division and generally predominates the
sympathetic system in “rest-and-digest” situations.

• Parasympathetic stimulation do not occur in a diffuse form as seen in

the sympathetic outflow, parasympathetic fibres innervating specific
organs such as the gut, heart, or eye are activated separately, and the
system functions to affect these organs individually.
 Overview of Autonomic Nervous System
• Table 1: Comparison of Sympathetic and Parasympathetic Nervous System
SYMPATHETIC PARASYMPATHETIC

Sites of origin Thoracic and lumbar region of the Brain and sacral area of the spinal
spinal cord, T 1-12, L 1-3 cord, Cr 3,7,9,10 ; S 2-4
Length and type of Short myelinated preganglionic, Long Long myelinated preganglionic, short
fibres nonmyelinated postganglionic nonmyelinated postganglionic

Preganglionic – fibres Extensive Minimal

branching
Distribution Wide Limited
Type of response Intense ramification(1:20)= Very diffuse Limited ramification(1:1)= Discrete
Discharge=generalized action discharge=affects specific effector
system, individually

Metabolism Catabolic in nature (expenditure of Anabolic in nature (conservation &

energy) restoration of energy)
Transmitter Noradrenaline (major) Acetylcholine
(neuroeffector) Acetylcholine (minor)
Stability of transmitter NA stable, diffuses for wider actions ACh-rapidly destroyed, effect is local

Important function Tackling stress and emergency Assimilation of food, conservation of

energy
Functions of the Autonomic nervous system

Fig. 5: Organization of the sympathetic and

parasympathetic divisions of the ANS. The left
panel shows the sympathetic division. The cell
bodies of sympathetic preganglionic neurons
(red) are in the intermediolateral
column of the thoracic and lumbar spinal cord
(T1-L3). Their axons project to paravertebral
ganglia (the sympathetic chain) and
prevertebral ganglia. Postganglionic neurons
(blue) therefore have long projections to their
targets.
The right panel shows the parasympathetic
division. The cell bodies of parasympathetic
preganglionic neurons (orange) are either in
the brain (midbrain, pons medulla) or in the
sacral spinal cord (S2-S4). Their axons project
to ganglia very near (or even inside) the end
organs. Postganglionic neurons (green)
therefore have short projections to their
targets.
(Courtesy Medical Physiology: A Cellular and
Molecular Approach updated 2e)
 Functions of the Autonomic nervous system
• Table 2: Sympathetic and Parasympathetic actions
 Cholinergic & Adrenergic receptors
• There 2 families of cholinoceptors
• Nicotinic (N)
• Muscarinic (M)
• They are distinguished based different affinities for agents that mimic
the action of ACh (cholinomimetic agents).
• Nicotine receptors binds strongly to nicotine but weakly to muscarine
• Muscarinic receptors show a strong affinity for muscarine but very
weak affinity for nicotine.
 Cholinergic & Adrenergic receptors
• Nicotinic ACh receptors fall into three main classes, the muscle,
ganglionic and CNS types.
• They are located in the CNS, the adrenal medulla, autonomic ganglia,
and neuromuscular junction (NMJ) in skeletal muscles.
• They divided into 2 subtypes:

• A. NM – located majorly at the neuromuscular junction (NMJ)

• B. NN – located in other places.

 Cholinergic & Adrenergic receptors
• There are G protein coupled

• Found on ganglia of the peripheral nervous system and

• The autonomic primarily on autonomic effector cells in heart, smooth

muscles & exocrine glands and certain areas of CNS.
• All blood vessels have muscarinic receptors although they lack cholinergic
innervations
• Divided into 5 sub types

• M1, M2, M3, M4, M5.

• The odd-numbered members of the group (M1, M3, M5.) couple with Gq to
activate the inositol phosphate pathway, while the

• Even-numbered receptors (M2, M4) act through Gi to inhibit adenylyl cyclase

and thus reduce intracellular cAMP
Cholinergic & Adrenergic receptors
Table 2: Muscarinic Receptor Subtypes
 Adrenergic receptors
• Adrenergic Receptors (Adrenoceptors) are the receptors of the sympathetic
nervous system.
• Two main families of receptors
• Designated α and β, base responses/potency to the adrenergic agonists adrenaline
(epinephrine), noradrenaline (norepinephrine), and Isoprenaline (isoproterenol).
• α: epinephrine ≥ norepinephrine >> Isoprenaline
• β: Isoprenaline > adrenaline > noradrenaline.
• Adrenergic receptors are all are typical G-protein-coupled receptors and each class
is associated with a specific second messenger system.
• Each family of receptor specific receptor subtypes
• Studies with agonists and antagonists have confirmed the existence of two main α-
receptor subtypes (α1 and α2)

• three β-receptor subtypes (β1, β2 and β3).

Adrenergic Receptors Cont’d

Fig. 4: Major effects mediated by α- and β-adrenoceptors

 Adrenergic receptors
Table 3: Characteristics of adrenoceptors
Adrenergic Receptors Cont’d

a
Minor component normally but may increase in heart rise.
a
Minor component normally but may increase in heart rise.
A, adrenaline; ISO, isoproterenol; NA, noradrenaline.
 Neurohumoral Transmission
• Neurohumoral transmission is a process by which nerves
transmit their message across synapses and neuroeffector
junctions by the release of humoral (chemical) messengers.

• Nerve impulses elicit responses in smooth, cardiac, and

skeletal muscles, exocrine glands, and postsynaptic neurons
by liberating specific chemical neurotransmitters.

• The neuroeffector junction is often called a synapse.

• synaptic transmission or synaptic cleft.

 Neurohumoral Transmission
• Criteria for a substance to be called a Neurotransmitter

Chemical messengers must meet 4 criteria to be considered

transmitters:

i. It is synthesized by a neuron locally.

ii. It is present in the presynaptic terminal and is released in

amounts sufficient to exert a defined action on a postsynaptic
neuron or effector organ.

iii. When given as a drug, it mimics the action of naturally

occurring transmitter in the body exactly.

iv. A specific mechanism exists for removing it.

Steps in neurohumoral
transmission
1. Impulse
conduction

2. Transmitter
release

3. Transmitter
action on
postjunctional/po
st-synaptic
membrane

4. Postjunctional
activity

5. Termination of
transmitter
action
 Sites of Drug Action
• Drugs act on ANS by either modifying or mimicking the
actions of autonomic neurotransmitters.

• The main processes that occur in a classical chemically

transmitting synapse provides a useful basis for
understanding the actions of the many different classes
of drug.

• By facilitating or blocking neurochemical transmission

 Sites of Drug Action Cont’d
1. Uptake of precursors
2. Synthesis of transmitter
3. Uptake/transport of transmitter into
vesicles
4. Degradation of surplus transmitter
5. Depolarisation by propagated action
potential
6. Influx of Ca2+ in response to
depolarisation
7. Release of transmitter by exocytosis
8. Diffusion to postsynaptic membrane
9. Interaction with postsynaptic
receptors
10. Inactivation of transmitter
11. Reuptake of transmitter or
degradation products by nerve
terminals
12. Uptake of transmitter by non-

Fig. 6: The main processes involved in neuronal cells; and

synthesis, storage and release of amine and 13. Interaction with presynaptic
amino acid transmitters receptors
 Sites of Drug Action Cont’d
• The transporters (11 and 12) can release transmitter
under certain conditions by working in reverse.

• These processes are well characterised for many

transmitters (e.g. acetylcholine, monoamines, amino
acids, ATP).

• Peptide mediators differ in that they may be synthesized

and packaged in the cell body rather than the terminals.
 Adrenergic Transmission
• Adrenergic drugs that activate adrenergic receptors are termed
sympathomimetics. Adrenergic neurons release norepinephrine as
the primary NT.
• Catecholamines
• Catecholamines are compounds containing a catechol moiety (a
benzene ring with two adjacent hydroxyl groups) and an amine side
chain.
 Adrenergic Transmission
• a) Noradrenaline (norepinephrine), a transmitter released by
sympathetic nerve terminals.
• b) Adrenaline (epinephrine), a hormone secreted by the adrenal
medulla.
• c) Dopamine, the metabolic precursor of noradrenaline and
adrenaline, also a transmitter/neuromodulator in the central
nervous system.
• d) Isoprenaline (also known as isoproterenol), a synthetic
derivative of noradrenaline, not present in the body.
 Adrenergic Transmission
• Neurotransmission at adrenergic neurons
• Neurotransmission in adrenergic neurons involves steps: synthesis,
storage, release, and receptor binding Catecholamines, followed by
removal of the neurotransmitter from the synaptic gap.

• Synthesis
• The starting product for the synthesis of catecholamines is tyrosine
and it is transported by a carrier into the adrenergic neuron.
 Adrenergic Transmission
Cont’d

(Vitamin B6)

(Vit C) & Cu

(Occurs only in the

adrenal medulla).

Fig. 6. Synthesis of Catecholamines

 Adrenergic Transmission

Fig. 7: Synthesis and Release of Catecholamines

 Adrenergic Transmission
• Removal/Termination of norepinephrine: The major process of termination of
the action of release NA is by reuptake into the neuron known as uptake I.
• The process can be by tricyclic antidepressants (TCAs) such as imipramine, by
serotonin–norepinephrine reuptake inhibitors and such as duloxetine, or by
cocaine.

• B. NA is by uptake in to the effector tissue. The process is call uptake II or

extraneuronal uptake.

• C. the transmitter may diffuse out of the synaptic space and enter the systemic
circulation and metabolized by Cathechol-O-methyltransferase (COMT).
 Adrenergic Transmission
• Potential fates of recaptured norepinephrine: Once norepinephrine
reenters the adrenergic neuron, it may be taken up into synaptic
vesicles via the amine transporter system uptake III (blocked by
reserpine)

• It may be sequestered for release by another action potential, or it

may persist in a protected pool in the cytoplasm.

• Alternatively, norepinephrine can be oxidized by monoamine oxidase

(MAO) present in neuronal mitochondria.
 Cholinergic Transmission
• The synthesis, storage, and release of ACh follow a similar life cycle in
all cholinergic synapses.
• This include those at
• Skeletal neuromuscular junctions, preganglionic sympathetic and
parasympathetic terminals
• Postganglionic parasympathetic varicosities,
• postganglionic sympathetic varicosities innervating sweat glands in
the skin,
• CNS where Ach is used as a neurotransmitter
 Cholinergic Transmission
• Two enzymes, choline acetyltransferase and Acetylcholinesterase
AChE, are involved in ACh synthesis and degradation, respectively.
Neurotransmission in cholinergic neurons involves six sequential
steps:
• I. Synthesis
• II. Storage
• III. Release
• IV. Binding of ACh to a receptor
• V. Degradation of the neurotransmitter in the synaptic cleft and
• VI. recycling of choline and acetate
 Cholinergic Transmission
• Acetylcholine is synthesized in a single step from choline and acetyl
coenzyme A (acetyl CoA) by the enzyme choline acetyltransferase
(ChAT):
 Cholinergic Transmission

Fig. 8: Schematic representations of a cholinergic neuroeffector junction showing features of the synthesis, storage, and release of acetylcholine (ACh) and receptors on which ACh acts.
Thank you