Autonomic Nervous System:

Organization, Neurotransmitters,
Functions and Regulations
PHARMACOLOGY
PGY 3310

M.Kampamba (DipPharm, Bpharm, MclinPharm) PhD Candidate

Clinical Pharmacy Specialist (Specialty: General Pharmacotherapy)

Full time lecturer University of Zambia
School of Health Sciences
School of Medicine
Learning Objectives:
Be able to:
1) Describe the functions of the sympathoadrenal (SAS) and
parasympathetic (PNS) systems of the Autonomic Nervous
system, and their interactions.
2) Name the major cholinoceptors and adrenoceptors of the
Autonomic Nervous System and identify their important
receptor subtypes.
3) Associate the actions of membrane receptor subtypes with
appropriate “second messenger” systems.
4) Describe the interplay of SAS and PNS
5) Explain Autonomic control of Blood Pressure

2
 Peripheral Nervous System
Somatic Nervous Autonomic Nervous
System System

Parasympathetic Sympathetic
Nervous System Nervous System

Discrete Diffuse
Activation Activation
Skeletal
Muscle
Glands, Smooth Muscle
& Cardiac Muscle 4
Question Time: True or False

1. Which one of the following is the component of autonomic

nervous system?
a. Afferent division
b. Efferent division
c. Sympathetic system
d. Somatic system
• The motor (efferent) portion of the nervous system can be
divided into two major subdivisions: autonomic and somatic.
• The autonomic nervous system (ANS) is largely autonomous
(independent) in that its activities are not under direct conscious
control.
• It is concerned primarily with function that occur without
conscious control which are necessary for life, functions
such as;
• Cardiac output, blood flow to various organs,
• Contraction and relaxation of smooth muscle
• All exocrine and certain endocrine secretions
• Certain steps in intermediary metabolism
DIVISION OF AUTONOMIC NERVOUS SYSTEM

• The autonomic nervous system lends itself to division on

anatomic grounds into two major portions:
• the sympathetic (thoracolumbar) division and
• the parasympathetic (craniosacral) division
• The autonomic efferent pathway consist of two neurons
arranged in series the preganglionic and postganglionic fibers.

• The two neurons synapse in autonomic ganglia which lie

outside the C.N.S and contain nerve endings of the
preganglionic fibers and cell bodies of the postganglionic
fibers.
• The sympathetic and parasympathetic systems have opposing actions for
example control of heart rate and gastrointestinal muscles.
• Sympathetic activity predominates in stress (fight or flight response).
• The parasympathetic system is organised for localised and discrete discharge
for example digestion and absorption.
• Parasympathetic system is concerned with energy conservation and
maintenance of organ function during periods of minimal activity.
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TRANSMITTERS OT THE AUTONOMIC NERVOUS SYSTEM

• The principal transmitters are acetylcholine and norepinephrine.

• Parasympathetic: Acetylcholine
• Sympathetic: Norepinephrine
ADRENERGIC TRANSMISSION

• Norepinephrine (NE) is the transmitter of all postganglionic

sympathetic neurons except those supplying the sweat glands and
piloerector muscle.
ADRENERGIC TRANSMISSION-

• adrenergic neurotransmitters (endogenous catecholamine)

• Norepinephrine (NE) - the transmitter of postganglionic sympathetic
fibers and certain C.N.S tracts.
• Epinephrine (EP) – the major hormone of the adrenal medulla
• Dopamine (DA) – the predominant transmitter of the extrapyramidal
tract and several mesocortical and mesolimbic neuronal pathways
 SYNTHESIS OF CATECHOLAMINES
TYROSINE
Tyrosine hydroxylase
DOPA
Dopa decarboxylase
DOPAMINE
Dopamine beta
hydroxylase
NOREPINEPHRINE
N-methyltransferase
EPINEPHRINE
  NOREPINEPHRINE STORAGE

• NE is stored in synaptic vesicles at the terminal end of

adrenergic neurons.
• The vesicles contain Norepinephrine, adenosine triphosphate
(ATP) and chromogranin-A which are released with NE
 NOREPINEPHRINE RELEASE

• Release of transmitter occurs when the voltage-sensitive calcium channels

in the terminal membrane are opened, allowing an influx of calcium

• The resulting increase in intracellular calcium causes fusion of vesicles

with the surface membrane and exocytosis expulsion of NE and
cotransmitters into the junctional cleft.

• The transmitter then activates the alpha and beta adrenergic receptors in
the membrane of the postsynaptic cells.
UPTAKE OF CATECHOLAMINES
Neuronal uptake

• the main mechanism by which the released Norepinephrine is

inactivated. It is relatively selective for Norepinephrine
ENZYMATIC DEGRADATION OF CATECHOLAMINES

• Circulating NE and EP are degraded enzymatically by monoamine

oxidase (MAO) enzyme and catechol-o-methyl transferase (COMT)
enzyme.

• MAO is abundant in adrenergic nerve terminals. It is also present in

brain, liver, intestine and kidney

• NE released within the nerve terminal is metabolised by MAO

enzyme

• COMT, particularly in the liver, plays a major role in the metabolism

of endogenous circulating and administered catecholamines.
CLASSIFICATION OF ADRENERGIC RECEPTORS

1. Alpha adrenergic receptors (α1 and α2).

2. Beta adrenergic receptors (β1and β2)
ALPHA (α) ADRENERGIC RECEPTORS
• ALPHA1 (α1) ADRENERGIC RECEPTORS
• Vasoconstriction
• Contraction of dilator papillae muscle causing active mydriasis
• Contraction of sphincters
• Intestinal relaxation
• Liver glycogenolysis and potassium release
ALPHA2 (α2) ADRENERGIC RECEPTORS;

Are present presynaptically and postsynaptically.

• Presynaptic α2 Receptors mediate presynaptic inhibition of norepinephrine
release from sympathetic nerves.

Postsynaptic α2 receptors
• Decrease central sympathetic outflow
• Inhibition of lipolysis
• Inhibition of insulin secretion which is the predominant effect
• Stimulation of platelet aggregation
Question Time : True or false
1. Which one of the following pharmacological effects will be as the result of
blocking alpha-1 adrenergic receptors?
a. mydriasis
b. Vasodilation
c. Relaxation of sphincters
d. Intestinal relaxation

2. Which one of the following pharmacological effect is mediated by

stimulation of alpha-2 adrenergic receptors?
a. Hyperglyceamia
b. vasoconstriction
c. Stimulating lipolysis
d. Inhibition of platelet aggregation
BETA (β) ADRENERGICRECEPTORS

• Β1 ADRENERGIC RECEPTORS (excitatory)

• Cardiac stimulation
 positive inotropic, chronotropic and dromotropic
 Increase cardiac output
• Lipolysis increasing free fatty acids in blood
• Increase rennin secretion
BETA 2 ADRENERGIC RECEPTORS

• Bronchodilation and mast cell stabilisation

• Vasodilatation
• Intestinal and uterine relaxation
• Hypokalaemia , Hyperglycemia due to liver and muscle glycogenolysis
• Stimulate insulin release
• Skeletal muscle tremors
CHOLINERGIC TRANSMISSION
• Acetylcholine is the transmitter of;
• All preganglionic efferent autonomic fibers, sympathetic and parasympathetic
• Preganglionic fibers (greater splanchnic nerve) to the adrenal medulla which can
be considered as modified sympathetic ganglion
• All the somatic (nonautonomic) motor fibers to skeletal muscle
release acetylcholine at the neuromuscular junction
• parasympathetic postganglionic neurons
• sympathetic postganglionic fibers to sweat glands and
piloerector muscle
Synthesis of Acetylcholine (Ach):

• Cholinergic fibers synthesize Ach by acetylation of choline which is transported

by a membrane carrier from the extracellular fluid into the neuronal terminal.
• In the cytoplasm, choline acetyl transferase catalyses acetylation of choline by
Acetyl CoA resulting in formation of acetylcholine
Drugs interfering with synthesis of Ach:
• Hemicholinium and Tri-ethylcholine compete with
choline uptake.

Storage of Ach:
• Ach is stored together with ATP and Ca++ in small
membrane-bound vesicles which are concentrated in
the terminals of cholinergic neurons.
.
Release of Ach:
• The action potential triggers the influx of Ca++ which stimulates a
contractile protein that pulls the vesicle towards presynaptic membrane.
• Ach is then released by exocytotic expulsion

Drugs interfering with release of Ach

• Muscarinic agonists acting on presynaptic muscarinic receptors (M2).
• Mg++
• Aminoglycosides and Polymixin antibiotics block exocytotic expulsion of
vesicles by preventing Ca++ entry into the nerve terminal
Hydrolysis of Ach:
• Ach is hydrolysed by choline esterase enzymes.
• hydrolysed into choline and acetylated enzyme.
 Mechanism of action of Ach:
• Ach acts by activation of muscarinic or nicotinic receptors.

Muscarinic receptors are G-protein coupled:

• M1, M3, M5 subtypes are linked to Gp protein leading to activation of
phospholipase-C enzyme which causes the generation of two second
messengers; Inositol triphosphate (IP3) and diacylglycerol (DAG) leading to
increase in the intracellular Ca++ concentration
• M2 and M4 receptors are linked to G-inhibitory protein leading to inhibition of
adenyl cyclase enzyme resulting in decreased intracellular concentration of
cAMP and inhibition of protein kinase-A.
• M2 receptors also increase K+ conductance and cause mediation of Ca++
channel activity

• Nicotinic receptors are ligand-gated ion channels; they are pentamers that
extend through cell membrane around a sodium channel
Summary of Sympathetic and Parasympathetic

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• END OF LECTURE
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