Effect of cyclic nucleotide derivatives on the release of ACh from cortical slices of the rat brain.

Atropine (5 nM to 5 muM), but not D-tubocurarine or hexamethonium, enhanced the release of acetylcholine (ACh) from rat brain cortical slices exposed to high K+. The enhancement was dose-dependent, and it could be partially antagonized by oxotremorine (50-500 muM) or by dibutyryl or 8-bromo-cyclic GMP (1 mM), but not by tetrodotoxin (200 nM) or by dibutyryl cyclic AMP (1 mM). The effects of oxotremorine and the cyclic GMP derivatives were not due to diminished ACh synthesis, since these compounds did not influence the reduction of tissue ACh resulting from treatment with K+ and atropine. These results suggest that cyclic GMP may mediate the regulation of ACh release by presynaptic muscarinic receptors.