Smooth muscle cells isolated from the gastric muscle layers of the guinea pig were used to examine the functional endothelin receptor subtype responsible for gastric smooth muscle contraction by endothelin. Endothelin-1 induced the contraction of these cells in a dose-dependent manner, with an ED50 value of 0.2 nM. Endothelin-3-induced contraction was significantly less than that of endothelin-1. Sarafotoxin 6c (10(-11)-10(-7) M), endothelinB highly selective agonist, did not elicit the contraction of gastric smooth muscle cells. BQ-123, endothelinA selective antagonist, inhibited the contractile response produced by 10(-7) M endothelin-1 in a dose-dependent manner, with an IC50 value of 5 nM. These results strongly suggest that endothelin elicited the contraction of gastric smooth muscle cells via functional endothelinA receptor subtype.