Prostaglandin E 2 induced the cyclic AMP-dependent release of acetylcholine in circular muscles of the isolated guinea pig ileum

Abstract

Prostaglandin E 2 (PGE 2) induced a dose-dependent increase in tone of the circular muscles of guinea pig ileum in vitro. These actions of PGE 2 were deleted in the cold-stored preparations and blocked by tetrodotoxin. Atropine reduced the effects of PGE 2 and physostigmine potentiated the PGE 2-induced contractions. The release of acetylcholine (ACh) by PGE 2 was responsible for initiating this contraction. The effect of PGE 2 was compared with that of an electrical stimulation which also initiated a non-receptor-mediated release of ACh. Hexamethonium abolished the effect of PGE 2 but did not influence the actions of the electrical stimulations. Synaptosomal fractions of the circular muscles were prepared to study the release of [ 14C]ACh. However, PGE 2 failed to evoke a marked increase in the efflux of radioactivity, even at the maximal concentration. Damage and/or removal of the myenteric plexus may be responsible for this result because electrical stimulations that exert a powerful spasmogenic effect on longitudinal muscles also induced an insensitive response. Alloxan and ethacrynic acid, inhibitors of adenylate cyclase, reduced the activity of PGE 2 at a concentration insufficient to modify either the actions of ACh or the electrical stimulations. 3-Isobutyl-1-methylxanthine (IBMX) potentiated the responses to PGE 2 at a dose sufficient to block the activity of phosphodiesterase (PDE). Imidazole, a stimulator of PDE, decreased the actions of PGE 2 in a dose-dependent manner. IBMX, like imidazole, failed to modify the activities of both ACh and the electrical stimulations. These results indicate that PGE 2 may function as a releaser of ACh in a cyclic AMP-dependent manner in the circular muscles of guinea pig ileum.