Effects of Adenylate Cyclase Inhibitors, Phosphodiesterase Inhibitors, and Dibutyryl Cyclic AMP on Spontaneous and Various Stimuli-lnduced Acetylcholine Release from Guinea Pig Ileum Myenteric Plexus

Abstract

In order to examine a possible contribution of cyclic AMP to acetylcholine (ACh) release from guinea pig ileum myenteric plexus, effects of adenylate cyclase inhibitors, phosphodiesterase (PDE) inhibitors and dibutyryl cyclic AMP on the spontaneous and the various stimuli-induced ACh release were investigated. A PDE inhibitor, theophylline (1 mM) increased the ACh release induced by nicotine (6.16 microM) significantly. Another PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 1 mM) and dibutyryl cyclic AMP (4 mM) had no effect. The adenylate cyclase inhibitors dithiobisnitrobenzoic acid (DTNB, 1 mM) and alloxan (4 mM) both decreased the nicotine-induced ACh release remarkably. PDE inhibitors increased and adenylate cyclase inhibitors decreased the high-K+-induced ACh release. Dibutyryl cyclic AMP brought about a slight but significant increase of the high-K+-induced ACh release. All the drugs failed to alter the ACh release induced by electrical field stimulation (EFS) at 10 Hz. Effects of all drugs except dibutyryl cyclic AMP on the spontaneous ACh release were the same as those on the nicotine-induced one. Dibutyryl cyclic AMP decreased it significantly. These results suggest that the cyclic AMP system is involved in the spontaneous, the nicotine-induced and the high-K+-induced ACh release and that the EFS-induced ACh release is independent of cyclic AMP.