PRESYNAPTIC MUSCARINIC RECEPTORS MODULATE ACETYLCHOLINE-RELEASE FROM RAT ANTRAL MUCOSAL SUBMUCOSAL NERVES/

The purpose of the present studies was to determine whether autoinhibi tion of acetylcholine release could be demonstrated in vitro from muco sal/submucosal neurons in rat antrum. Rat antral mucosal/submucosal ti ssues preloaded with [H-3]choline were perifused and [H-3]acetylcholin e release measured under basal and stimulated conditions. Carbachol in hibited both spontaneous and evoked (electrical field stimulation, KCl ) acetylcholine release from rat antral tissues: 1 x 10(-5) M carbacho l inhibited basal [H-3]ACh release maximally to - 38.2 +/- 3.1% (P < 0 .001 vs control). The nonselective muscarinic antagonist atropine enha nced both basal and stimulated acetylcholine release and abolished car bachol-induced inhibition of acetylcholine release. Pirenzepine, a mus carinic M(1) receptor antagonist, inhibited acetylcholine release and did not alter carbachol-induced inhibition of acetylcholine release. I n conclusion, acetylcholine release from rat antral mucosal/submucosal neurons is regulated negatively by a presynaptic feedback mechanism i nvolving M(2) and/or M(3) receptors, while presynaptic M(1) receptors facilitate release of neurotransmitter.