Effects of H-89, an inhibitor of protein kinase A, on the acetylcholine release from myenteric plexus of guinea pig ileum

Abstract

In order to clarify the involvement of cyclic AMP-dependent protein kinase (protein kinase A) in acetylcholine (ACh) release from myenteric plexus of guinea pig ileum, the effect of H-89, a specific inhibitor of protein kinase A, on the ACh release was investigated. H-89 (0.1-10μM) inhibited the spontaneous and nicotine-induced release of ACh in a concentration dependent manner. It at 1μM decreased both kinds of release of ACh to almost half of the control, but it did not affect the ACh release evoked by electrical field stimulation and by 5-hydroxytryptamine. H-89 had no significant effect on the indomethacin (IND), an inhibitor of PG synthesis, -insensitive component of the spontaneous and nicotine-induced release of, ACh. OP-41483, an analog of PGI, and forskolin, an activator of adenylate cyclase, reversed the inhibitory effect of IND on the ACh release. H-89 at 1μMcompletely inhibited the reverse effects of OP-41483 and forskolin. These results suggest that activation of protein kinase A is essential for modulation of the nicotineinduced and spontaneous ACh release from myenteric plexus of guinea pig ileum and the activity of protein kinase A is regulated by endogenous PGs via intracellular cyclic AMP level.