Presynaptic muscarinic receptors modulate acetylcholine release from rat antral mucosal/submucosal nerves

The purpose of the present studies was to determine whether autoinhibition of acetylcholine release could be demonstrated in vitro from mucosal/submucosal neurons in rat antrum. Rat antral mucosal/submucosal tissues preloaded with [3H]choline were perifused and [3H]acetylcholine release measured under basal and stimulated conditions. Carbachol inhibited both spontaneous and evoked (electrical field stimulation, KCl) acetylcholine release from rat antral tissues: 1 x 10(-5) M carbachol inhibited basal [3H]ACh release maximally to -38.2 +/- 3.1% (P < 0.001 vs control). The nonselective muscarinic antagonist atropine enhanced both basal and stimulated acetylcholine release and abolished carbachol-induced inhibition of acetylcholine release. Pirenzepine, a muscarinic M1 receptor antagonist, inhibited acetylcholine release and did not alter carbachol-induced inhibition of acetylcholine release. In conclusion, acetylcholine release from rat antral mucosal/submucosal neurons is regulated negatively by a presynaptic feedback mechanism involving M2 and/or M3 receptors, while presynaptic M1 receptors facilitate release of neurotransmitter.