Involvement of endothelin receptor subtypes in human myometrial activity

We investigated the contribution of endothelin (ET) ETA and ETB receptors to ET-induced contractions of human myometrium and their distribution in cultured myometrial cells. ET-1 was more potent than ET-3 in evoking concentration-dependent increases in smooth muscle tension. A selective ETB agonist, BQ 3020, was inactive in eliciting contractions. In myometrial cell membranes, no specific [125I]ET-3 binding was observed. Inhibition of [125I]ET-1 binding by unlabeled compounds showed the following order of potency: ET-1 = FR 139317 > ET-3 >> S6c. Furthermore, ET-1 increased inositol phosphate (IP) production in a dose-dependent manner. ET-1-induced IP accumulation was totally abolished by FR 139317 (an ETA-selective antagonist) but was not altered by IRL 1038 (an ETB-selective antagonist). These results indicate that only ETA receptors, which mediate ET-1-induced uterine contraction, are present in cultured myometrial cells.