Atypical receptors mediate the response to endothelin-1 and sarafotoxin S6b in the human umbilical artery

Abstract

The receptors mediating smooth muscle response to endothelin-1 and sarafotoxin S6b in the human umbilical artery were investigated in vitro. Both agonists induced contractions that were unaffected by the endothelin ET B receptor antagonist BQ 788 (10 −9, 10 −8, 10 −7 M). The non-selective endothelin ET A/B receptor antagonist PD 142893 (10 −7 M) decreased the contraction induced by endothelin-1. PD 142893 (10 -9 M) enhanced the contraction induced by sarafotoxin S6b whereas higher concentrations had no effect. Removing the endothelium did not affect the antagonising action of PD 142893 on endothelin-1-induced contractions while the enhancement of the sarafotoxin S6b-induced contraction was abolished. Sarafotoxin S6b induced relaxation in segments precontracted by 5-hydroxytryptamine and exposed to the endothelin ET A receptor antagonist BQ 123 (10 −7 M) and PD 142893 (10 −9 M) abolished this relaxation. These endothelial receptors seem neither to be classical endothelin ET A nor endothelin ET B receptors and they are not activated by endothelin-1.