Veterinary Neuropharmacology

SYNTHESIS, STORAGE AND DESTRUCTION OF ACETYLCHOLINE

• Acetylcholine is synthesized locally in the cholinergic nerve endings by the following pathway.                       

            

• Choline is actively taken up by the axonal membrane and acetylated with the help of ATP and coenzyme-A by the enzyme choline acetylase present in the axoplasm.
• Uptake of choline is the rate limiting step. This uptake is blocked by Hemicholinium and depletes acetylcholine.
• Most of the acetylcholine is stored in ionic solution within small synaptic vesicles. But some free acetylcholine is also present in the cytoplasm of cholinergic terminals.
• Transport of acetylcholine into the synaptic vesicles is blocked by the drug vesamicol.
• Depolarization permits the influx of Ca⁺⁺. This Ca⁺⁺ facilitates the fusion of axonal and vesicular members at active zones resulting in extrusion of the contents. Ca⁺⁺ ionophores can also stimulate release of acetylcholine. Mg ⁺⁺ inhibits the relase of acetylcholine.
• Release of acetylcholine from the nerve terminals occurs in small quanta – amount contained in individual vesicles is extruded by exocytosis. In response to a nerve action potential, synchronous release of multiple quanta triggers postjunctional events.
• Two toxins,  Botulinum toxin inhibits release and causes paralysis. Black widow spider venom induces massive release.
• Immediately after release, acetylcholine is hydrolysed by the enzyme cholinesterase.

• It is stated that acetylcholine is removed in a flash like suddenness.
• Hydrolysis of acetylcholine produces choline and acetate.
• Choline is actively taken up into the prejunctional nerve cell and recycled. There are two types of acetylcholinesterases viz., True and Pseudo acetylcholinesterases.