MODULATION OF RELEASE OF [H-3] ACETYLCHOLINE IN THE MAJOR PELVIC GANGLION OF THE RAT

Cholinergic modulation of [H-3]acetylcholine release evoked by electri cal stimulation was studied in the rat major pelvic ganglion, which wa s prelabeled with [H-3]choline. Acetylcholine (ACh) release was indepe ndent of the frequency of stimulation; 0.3 Hz produced the same volley output as 10 Hz. Tetrodotoxin (1 muM) or omission of Ca2+ from the me dium abolished ACh release. The M1 receptor agonist (4-hydroxy-2-butyn yl)-l-trimethylammonium m-chlorocarbanilate chloride (McN-A 343, 50 mu M) increased release (by 136%), whereas the M2 muscarinic agonist oxot remorine (1 muM) decreased ACh release (by 22%). The muscarinic antago nists, atropine (1 muM) or pirenzepine (M1 selective, 1 muM), did not change ACh release. However, pirenzepine (1 muM) blocked the facilitat ory effect of McN-A 343, and atropine (1 muM) blocked the inhibitory e ffect of oxotremorine. The cholinesterase inhibitor physostigmine (1-5 muM), the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10 muM), and the nicotinic antagonist D-tubocurarine (50 muM) did not change ACh release. 4-Aminopyridine, a K- channel blocker, significant ly increased the release (by 146%). Seven days after decentralization of the major pelvic ganglion, the evoked release of ACh was abolished. It is concluded that release of ACh occurs from the preganglionic ner ve terminals rather than from the cholinergic cell bodies and is not m odulated by actions of endogenous ACh on either muscarinic or nicotini c autoreceptors. These data confirm and extend previous electrophysiol ogical findings indicating that synapses in the major pelvic ganglion have primarily a relay function.