Stimulation of acetylcholine release from myenteric neurons of guinea pig small intestine by forskolin and cyclic AMP

WM Yau, JA Dorsett and ML Youther

Department of Medical Physiology and Pharmacology, School of Medicine, Southern Illinois University, Carbondale.

Forskolin, an activator of adenylate cyclase, was used to examine the regulation of [3H]acetylcholine (ACh) release by cyclic AMP (cAMP)- related mechanisms in myenteric plexus-longitudinal muscle preparations of guinea pig small intestine. Forskolin evoked a dose-related increase in [3H]ACh release. Both dibutyryl-cAMP and 8-Br-cAMP significantly elevated [3H]ACh secretion. In the presence of phosphodiesterase inhibitors (theophylline and 3-isobutyl-1-methylxanthine), the basal [3H]ACh output was increased. There was a significantly greater stimulation when forskolin was used to incite endogenous cAMP synthesis and phosphodiesterase inhibitors were simultaneously applied to prevent cAMP breakdown. The enhancement of forskolin-stimulated release by theophylline or 3-isobutyl-1-methylxanthine strongly implicates a synergistic interaction between the two. These findings suggest that forskolin acts to increase ACh release by a modulation of endogenous cAMP and further support a cAMP-mediated mechanism in the secretion of ACh from myenteric cholinergic neurons.

Volume 243, Issue 2, pp. 507-510, 11/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics

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