Cholinergic Transmission

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Chapter: Essential pharmacology : Cholinergic System And Drugs

Acetylcholine (ACh) is a major neurohumoral transmitter at autonomic, somatic as well as central sites.


CHOLINERGIC TRANSMISSION

 

Acetylcholine (ACh) is a major neurohumoral transmitter at autonomic, somatic as well as central sites. These sites are listed in Table 7.1

 

Synthesis, Storage And Destruction Of Ach



 

The cholinergic neuronal mechanisms are summarized in Fig. 7.1.


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

 


 

Choline is actively taken up by the axonal membrane by a Na+: choline cotransporter and acetylated with the help of ATP and coenzyme-A by the enzyme choline acetyl transferase present in the axoplasm. Hemicholinium blocks choline uptake (the rate limiting step in ACh synthesis) and depletes ACh. Most of the ACh is stored in ionic solution within small synaptic vesicles, but some free ACh is also present in the cytoplasm of cholinergic terminals. Active transport of ACh into synaptic vesicles is effected by another carrier which is blocked by vesamicol.

 

Release of ACh from nerve terminals occurs in small quanta—amount contained in individual vesicles is extruded by exocytosis. In response to a nerve AP synchronous release of multiple quanta triggers postjunctional events.

 

Two toxins interfere with cholinergic transmission by affecting release: botulinus toxin inhibits release, while black widow spider toxin induces massive release and depletion. Immediately after release, ACh is hydrolyzed by the enzyme cholinesterase and choline is recycled.

 

A specific (Acetylcholinesterase—AChE or true cholinesterase) and a nonspecific (Butyrylcholinesterase—BuChE or pseudocholinesterase) type of enzyme occurs in the body; important differences between these two types are given in Table 7.2. While AChE is strategically located at all cholinergic sites and serves to inactivate ACh instantaneously, BuChE present in plasma and elsewhere probably serves to metabolize ingested esters.


 

 



 

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