Contractile actions of endothelins in rat gastric body: evidence for receptor subtypes and involvement of prostaglandin E2.

Endothelin-1 produced a phasic contraction in the longitudinal muscle preparation isolated from the rat gastric body, but produced a sustained contraction in the circular muscle preparation. Indomethacin, a cyclo-oxygenase inhibitor, decreased the endothelin-1-induced contraction of the longitudinal preparation, but did not affect the endothelin-1-induced contractions of the circular muscle. In the absence of indomethacin, the maximal contractile tension (Emax) and the concentration producing a half-maximal contraction (EC50) induced by endothelin-3 in the longitudinal muscle preparations were smaller than those for endothelin-1, whereas in the circular muscle preparations there were no significant differences between the values (EC50, Emax) for endothelin-1 and endothelin-3. In the presence of indomethacin, endothelin-3-induced contraction of the longitudinal muscle preparation is more potent than that of endothelin-1. SC-19220, a prostaglandin E2 receptor antagonist, significantly decreased endothelin-1-induced contraction of the longitudinal preparation, prostaglandin E2 produced a concentration-dependent contraction in the longitudinal preparation, but had no effects in the circular muscle preparation. Endothelin-1 (10(-8) M) significantly increased the release of immunoassayable prostaglandin E2 from rat gastric smooth muscle. These results point to the existence of distinct endothelin receptor subtypes in the smooth muscle of rat gastric body, and a potential role of endothelin-1 in regulating gastric motility. Moreover, one of the endothelin receptor subtypes is related to the production of prostaglandin E2.