CONTRACTILE ACTIONS OF ENDOTHELINS IN RAT GASTRIC BODY - EVIDENCE FORRECEPTOR SUBTYPES AND INVOLVEMENT OF PROSTAGLANDIN E(2)

Endothelin-1 produced a phasic contraction in the longitudinal muscle preparation isolated from the rat gastric body, but produced a sustain ed contraction in the circular muscle preparation. Indomethacin, a cyc lo-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 indomet hacin, the maximal contractile tension (E(max)) and the concentration producing a half-maximal contraction (E(50)) induced by endothelin-3 i n the longitudinal muscle preparations were smaller than those for end othelin-1, whereas in the circular muscle preparations there were no s ignificant differences between the values (EC(50), E(max)) for endothe lin-1 and endothelin-3. In the presence of indomethacin, endothelin-3- induced contraction of the longitudinal muscle preparation is more pot ent than that of endothelin-1. SC-19220, a prostaglandin E(2) receptor antagonist, significantly decreased endothelin-l-induced contraction of the longitudinal preparation prostaglandin E(2) produced a concentr ation-dependent contraction in the longitudinal preparation, but had n o effects in the circular muscle preparation. Endothelin-1 (10(-8) M) significantly increased the release of immunoassayable prostaglandin E (2) from rat gastric smooth muscle. These results point to the existen ce of distinct endothelin receptor subtypes in the smooth muscle of ra t gastric body, and a potential role of endothelin-1 in regulating gas tric motility. Moreover, one of the endothelin receptor subtypes is re lated to the production of prostaglandin E(2).