INTRODUCTION TO AUTONOMIC NERVOUS SYSTEM (ANS)
Introduction to ANS
It is one of the two systems for control and integration of body functions. The other system is the
Divisions of the nervous systems:
A. Central nervous system: consists of
2. Spinal cord
B. Peripheral nervous system:
1. Somatic nervous system:
Under direct control of will. Concerned with conciously controlled functions, e.g.
locomotion, as well as respiration and posture.
It consists of:
Cranial nerves – 12 pairs
ii. Spinal nerves – 31 pairs
2. Autonomic nervous system:
It is not under direct control of will. Concerned with visceral functions, e.g. cardiac
output, blood flow to various organs, digestion, elimination, etc.
It consists of:
Sympathetic nervous system (Thoraco-lumbar system or Adrenal system)
ii. Parasympathetic nervous system (Cranio-sacral system or Cholinergic system)
Study of those drugs that affect:
Autonomic nervous system itself
Autonomic receptors on effector cells controlled by ANS (e.g. cardiac muscle, smooth
muscle, endothelial cells, and glands)
Neurotransmitter aspects of the ANS
Synthesis, storage, release, receptor interactions, and termination of action of the
neurotransmitters all contribute to the action of autonomic drugs.
Acetycholine (ACh) is the primary transmitter in all autonomic ganglia and at the synapses
between parasympathetic postganglionic neurons and their effector cells.
Transmitter at postganglionic sympathetic neurons to the thermoregulatory sweat glands.
Primary transmitter at the somatic (voluntary) skeletal muscle neuromuscular junction.
1) Synthesis and storage
a) Synthesised in the nerve terminal by enzyme choline acetyltransferase (ChAT)
from acetyl CoA (produced in mitochondria) and choline (transported across cell
b) Transport of choline from outside the membrane to inside can be inhibited by the
research drug hemicholinium.
c) ACh is actively transported into vesicles for storage. This process can be inhibited by
another research drug, vesamicol.
2) Release of acetylcholine
a) Release of ACh from vesicles at the nerve ending requires entry of calcium through
calcium channels. This process can be blocked off by botulinum toxins.
3) Termination of action of ACh
a) Action of ACh in the synapse is normally terminated by metabolism to acetate and
choline by the enzyme acetylcholinesterase in the synaptic cleft.
b) Products are not excreted by recycled in the body.
c) Inhibition of AChE is an important therapeutic (and potentially toxic) effect of
Norepinephrine (NE) the primary transmitter at the sympathetic postganglionic neuroneffector cell synapses in most tissues.
Important exceptions include sympathetic fibers to thermoregulatory (eccrine) sweat glands
and probably vasodilator sympathetic fibers in skeletal muscle, which release ACh.
Dopamine may be a vasodilator transmitter in renal blood vessels, but norepinephrine is a
vasoconstrictor of these vessels.
1) Synthesis and storage
a. After transport across cell membrane, tyrosine is hydroxylated by tyrosine
hydroxylase (the rate-limiting step) to DOPA (dihydroxyphenylalanine),
decarboxylated to dopamine, and (inside the vesicle) hydroxylated to NE.
b. Tyrosine hydroxylase can be inhibited by metyrosine.
c. Storage of dopamine into vesicles can be inhibited by reserpine, resulting in
depletion of transmitter stores.
2) Release and termination of action
a. Dopamine and NE released from nerve endings by same calcium-dependent
mechanism responsible for release of acetylcholine release.
b. Metabolism is not responsible for termination of action of the catecholamine
transmitters, NE and dopamine. Rather, diffusion and reuptake reduce their
concentrations in the synaptic cleft and stop their actions.
c. Outside the cleft, these transmitters are metabolised by enzymes and their products
d. Release of NE can be inhibited by guanethidine.
e. Reuptake can be blocked by cocaine and tricyclic antidepressants.
Actions of sympathetic and parasympathetic nervous systems on effector organs
Red= sympathetic actions (red means alert, danger, flight fight fright mode)
Blue= parasympathetic actions (blue means rest digest, calm and peaceful mode)
Contration of iris radial muscle (pupil dilates= mydriasis) (darr mein aapko zada dekhna
hota hai bhaagne ke liye :P )
Contraction of iris sphincter muscle (pupil contracts= miosis)
Stimulation of tears
Thick, viscous secretion (moun sookh jata hai darr mein)
Copious, watery secretion
Increased rate; increased contractility (heart starts beating fast when stressed and afraid)
Decreased rate; decreased contractility (sukun mein ho)
TRACHEA AND BRONCHIOLES
Dilation (darr mein saansen barh jaati hain :D )
Constriction, increased secretions
Secretion of epinephrine and norepinephrine
Decreased muscle motility and tone; contraction of spincters
Increased muscle motility and tone
Secretion of renin (β1 increases; α1 decreases)
URETERS AND BLADDER
Relaxation of detrusor; contraction of trigone and sphincter (darr mein bathroom bhaagne
ke khyalat ghanta nai aate)
Contraction of detrusor; relaxation of trigone and sphincter (happy bathroom )
Stimulation of ejaculation
Stimulation of erection
Relaxation of uterus
BLOOD VESSELS (SKELETAL MUSCLE)
BLOOD VESSELS (SKIN, MUCOUS MEMBRANES, AND SPLANCHNIC AREA)
Constriction (you get pale when scared)
Characteristics of sympathetic and parasympathetic systems
Sites of origin Thoracic and lumbar region
of the spinal cord (thoracolumbar)
Length of fibers Short preganglionic
Location of ganglia Close to spinal cord
Preganglionic fiber Extensive
Type or response Diffuse
Brain and sacral area of
spinal cord (cranio-sacral)
Within or near effector
Major receptor systems in the ANS include:
3) Dopamine receptors
1) Muscarinic receptors:
Agonist: muscarine, ACh
a) M1: located in CNS, sympathetic postganglionic neuron (at sympathetic ganglia),
gastric parietal cells, some presynaptic sites
b) M2: located in CNS, end-organs (e.g. myocardium, smooth muscle, eccrine or
thermoregulatory sweat glands, skeletal muscle blood vessels), some presynaptic sites
2) Nicotinic receptors:
Agonists: ACh, nicotine,
Antagonists: d-tubocurarine (blocks at autonomic ganglia and skeletal muscle),
hexamethonium (blocks at autonomic ganglia)
a) Spinal cord
b) Autonomic ganglia (sympathetic + parasympathetic)
c) Skeletal muscle NMJ
a) NG: located in autonomic ganglia
b) NM: located in skeletal muscle
Agonists: acc. to potency of action= epinephrine ≥ norepinephrine > isoproterenol
Antagonists: phentolamine, phenoxybenzamine
a) Alpha-1: blocked by prazosin. Located postsynaptically in radial muscle of eye, heart,
most vascular smooth muscle, bronchial glands, GIT, rat liver, splenic capsule,
urinary bladder, pilomotor smooth muscle
b) Alpha-2: not blocked by prazosin and isoproterenol is ineffective on them.
i. Presynaptically on adrenergic and cholinergic nerve terminals
ii. Postsynaptically on platelets, lipocytes, some vascular smooth muscles (noninnervated), brain
Agonists: acc. to potency of action= isoproterenol > norepinephrine ≥ epinephrine
a) Beta-1: have equal affinity for epinephrine and norepinephrine
i. Presynaptically on noradrenergic nerve terminals
ii. Postsynaptically on heart, lipocytes, and kidneys.
b) Beta-2: have higher affinity for epinephrine than norepinephrine.
Located postsynaptically on following sites: bronchial smooth muscle, bronchial
glands, GIT wall, human liver, urinary bladder, pregnant uterus, skeletal muscle
Stimulated by dopamine.
Agonist: phenothiazine, butyrophenone
Extra-cerebral locations of dopaminergic receptors:
Presynaptically on terminals of nerves supplying heart, blood vessels, and GIT
Postsynaptically on effector organs, especially vascular smooth muscles of splanchnic,
coronary, and renal blood vessels.