Cholinergic modulation of the release of [3H]acetylcholine from synaptosomes of the myenteric plexus.

The purpose of these experiments was to determine if cholinergic agents affected the release of acetylcholine (ACh) from a synaptosomal preparation of the guinea pig ileum myenteric plexus. The synaptosomal preparation was first incubated with the precursor [3H]choline; subsequently, release of the stored [3H]ACh was measured. The release was decreased by oxotremorine or exogenous ACh plus hexamethonium and increased by exogenous ACh plus evoked release that was inhibited by nicotinic antagonists or muscarinic agonists. Release was stimulated half-maximally by approximately 2 microM- and maximally by 10 microM-DMPP. Either in the absence of calcium or at 0 degrees C, DMPP was without effect. The effect of 10 microM-DMPP was brief, a significant stimulation occurring only within the first 2 min at 37 degrees C. Tetrodotoxin also inhibited excitation by DMPP but not completely. Thus, the release of [3H]ACh appears to be presynaptically modulated, negatively by muscarinic agonists and positively by nicotinic agonists.