156 Section 3/ Drugs Acting on ANSACETYLCHOLINE
Acetylcholine (ACh) is an ester of
choline and acetic acid available in powder
form as chloride or bromide salt. It is
extremely hygroscopic and rapidly
undergoes hydrolysis in a neutral or alkaline
medium.
It is synthesized within the cholinergic
neurons by the transfer of an acetyl group
from acetyl coenzyme A to the organic base
choline. The specific enzyme ‘choline
acetylase’ is essential for this reaction.
Coenzyme A is widely distributed in the
body and choline acetylase is synthesized
in the cell bodies of the cholinergic neurons.
ACh is produced throughout the
neurone and is stored in synaptic vesicles
at the nerve endings.
There are two types of esterases found in
animal tissues. True cholinesterase which is
found in neural structures, RBC and placenta
and is concerned with destruction of
acetylcholine released at the nerve endings.
The second type is ‘pseudocholinesterase’
(non-specific cholinesterase) is found in
blood serum, intestines, liver and skin and is
responsible for the hydrolysis of
benzoylcholine and does not hydrolyse
methacholine. Cholinesterase hydrolyses
acetylcholine into choline and acetic acid.
Pharmacological Actions
Stimulation of the parasympathetic
nervous system modifies the organ functions
by two main pathways. Firstly, the
acetylcholine released from parasympathetic
nerves can activate muscarinic receptors
which are present in gland cells (sweat
glands), smooth muscles and heart. The
muscarinic action of acetylcholine are
stimulated by muscarine and are blocked by
atropine. Second, by its nicotinic action on
autonomic ganglia, motor end plates of
skeletal muscles and adrenal medulla etc.
The action of acetylcholine on autonomic
ganglia can be blocked by ganglion blocking
agents such as hexamethonium and action
on myoneural junction can be antagonised
by d-tubocurarine.Muscarinic Actions
Cardiovascular system: Acetylcholine
decreases the contractility (negative
inotropy) and decreases the conduction
velocity (negative dromotropy) of the atria.
It depresses the sinoauricular node,
decreases the heart rate (negative
chronotropy) and may cause cardiac arrest.
In isolated heart preparation,
acetylcholine reduces the cardiac rate and
in the presence of atropine, it can stimulate
the heart causing ventricular arrhythmias.
Acetylcholine dilates all blood vessels
causing flushing and fall in blood pressure. The
vasodilatation is mediated through the release
of endothelium dependent relaxing factor
(EDRF). The fall in blood pressure is because
of decrease in total peripheral resistance and
cardiac output in anaesthetized animals.
Effect on smooth muscles: Acetylcholine
causes increase in tone, amplitude of
contractions, peristalsis and secretory activity
of the gastrointestinal tract. It causes
contraction of smooth muscles of gall bladder
and relaxation of sphincters of gastrointestinal
and biliary tract.
It also causes contraction of detrusor
resulting in decrease in the capacity of the