Biosynthesis, Storage, Release and Metabolism of Acetyl choline along with cholinergic receptors

1. Parasympathomimetic Drugs (Unit-3)
Biosynthesis, storage, release and metabolism of
acetylcholine
Cholinergic Receptors: Muscarnic and Nicotinic
Lecture-1
Dr. Jasmine Chaudhary
Associate Professor
MMCP, Mullana

3. Nervous System
Peripheral
Nervous System
12 pairs cranial nerves
31 pairs spinal nerves
Central Nervous
System
(Brain and Spinal cord)
Somatic Nervous
System
(Voluntary control)
Autonomic
Nervous System
(InVoluntary control)
•Sympathetic and
Parasympathetic

4. Autonomic Nervous System
Sympathetic Nervous System
(Adrenaline and Nor Adr)
Sympathetic nerves
•Increase heart rate
•Constrict blood vessels
•Raise blood pressure
•Fight-or-flight response
Parasympathetic Nervous System
(Acetyl Choline)
Parasympathetic nerves
•Slow heart rate
•Increase peristalsis of intestines
•Increase glandular secretions
•Relax sphincters

5. Neurotransmitter
 Chemical agents which are responsible for transmission of nerve
impulses across most synapse and neuro-effector junction.
e.g. Amines:Acetyl Choline, Dopamine, Adrenaline
Amino acids: Glycine, GABA
Miscellaneous: Substance P
Synapse
 Synapse is a structure that permits a neuron (nerve cell) to
pass an electrical or chemical signal to another neuron or to
target cell

7.  Synthesized in nerve terminal by action of choline acetylase
on choline.
 Ach synthesized get stored in storage vesicles and each
storage vesicles contain 5000-10000ACh molecules.

8. Choline + Acetyl CoA
Choline acetylase/ Transferase
Acetyl Choline (Stored in vesicles)
AcetylCholinesterase
Choline +Acetic acid

9.  When any impulse reaches nerve terminal
 Depolarization (Change in action potential occurs)
 Opening of Calcium channel occurs leading to influx of Ca
ions inside the nerve terminal
 This increase in Ca ions leads to rupturing of storage
vesicles containingACh
 This released acetyl choline then act on cholinergic receptor

to initiate the action.
Ruptured storage vesicles again reshaped to store fresh
neurotransmitter

10. METABOLISM OF ACh

12. ACh acts on 2 receptors
Muscarnic
Nicotinic
Muscarnic receptors are subdivided into
 M1
 M2
 M3
 Nicotinic receptors are subdivided into
 Nm
 Nn

13. 

Stimulated by muscarine, on the basis of their ability to be
bound by natural occuring alkaloid from Amanita muscarine
mushrooms
These are G protein coupled receptor causing
 Activation of phospholipase c
 Inhibition of adenylate cyclase
 Activation of potassium channels
 Inhibition of calcium channels

14. M1 (Neuronal) M2 (Cardiac) M3
(Smooth/Glandular)
Location CNS, Gastric
parietal cell
Cardiac atria,
conducting
tissues
Exocrine gland,
Smooth muscles
Action Increase gastic
motility
Increased gastric
acid secretion
CNS excitation
Cardiac
inhibition
Decrease BP
Smooth muscle
contraction
Increased secretions
like salivary
Agonist Carbachol Carbachol Carbachol
Antagonist Atropine,
Pirenzipine
Atropine,
Gallamine
Atropine, HHSD
(Hexa hydro
siladiferol)
Nicotinic receptor are dose dependent and generally involved skeletal muscle
contraction.

15. On nicotinic receptor Nn
Ach (small dose) cause vasodilation and thus hypotension
Ach ( large dose)-----hypertension. Due to stimulation of
adrenal medulla and sympathetic ganglia
On Nm nicotinic receptor contraction of Skeletal muscle

17. Question Bank
• Give biosynthesis, storage, release and metabolism of acetyl choline
• Discuss cholinergic receptors with their role and distribution.
• Discuss pharmacological actions of acetyl choline.

18. References
•Kadam SS, Mahadik KR, Bothara KG. Principles of Medicinal Chemistry.
Volume 2, Nirali Prakashan, 6.1-6.10.
•Singh H, Kapoor VK. Medicinal and Pharmaceutical Chemistry. 3rd
Edition, 2013, Vallabh Prakashan, 222-234.