Cholinergic Neuroeffector Junction
Choline uptake is inhibited by hemicholinium. ACh is synthesized from choline and acetyl-CoA via choline acetyltransferase (ChAT) and accumulated in synaptic vesicles.
Presynaptic membrane depolarization opens voltage-dependent Ca2+ channels, and the influx of this ion causes fusion of the synaptic vesicle membranes with the presynaptic membrane, leading to exocytosis of ACh. Botulinum toxin interacts with synaptobrevin and other proteins to prevent ACh release.
Some cholinergic nerve endings have presynaptic autoreceptors for ACh that on activation may elicit a negative feedback of transmitter release.
Inactivation via acetylcholinesterase (AChE) is the major mechanism of termination of postjunctional actions of ACh.
AChE is a target for inhibitory drugs (indirect-acting cholinomimetics). Note that such drugs can influence cholinergic function only at innervated sites where ACh is released.
Reversible AChE inhibitors include edrophonium, physostigmine, and neostigmine. Irreversible AChE inhibitors include echothiophate, malathion, and parathion.
Postjunctional receptors (N and M) activated by ACh are major targets for both activating drugs (direct-acting cholinomimetics) and cholinoceptor blocking agents.
Cholinomimetics
Nicotinic: nicotine
Muscarinic: bethanechol, methacholine, pilocarpine
Muscarinic: bethanechol, methacholine, pilocarpine
Cholinoceptor Blockers
Nicotinic (NN): hexamethonium, mecamylamine
Nicotinic (NM): tubocurarine, atracurium, succinylcholine
Muscarinic: atropine, benztropine, glycopyrrolate, scopolamine
Nicotinic (NM): tubocurarine, atracurium, succinylcholine
Muscarinic: atropine, benztropine, glycopyrrolate, scopolamine