CHARACTERIZATION OF ENDOTHELIN RECEPTORS AND LOCALIZATION OF I-125 ENDOTHELIN-1 BINDING-SITES IN HUMAN UMBILICAL ARTERY

The mechanisms of endothelin-1-induced contractile response in the hum an umbilical artery were investigated in vitro. Autoradiography reveal ed I-125-endothelin-1 binding sites in the smooth muscle layer of the vessel wail. Endothelin-1 and sarafotoxin S6b induced concentration-de pendent contractions while endothelin-3 was virtually without contract ile effect. The endothelin ET(A) receptor antagonist BQ 123 did not af fect the contraction to endothelin-1 but antagonized the contraction t o sarafotoxin S6b. The contraction to endothelin-1 and sarafotoxin S6b was diminished by both verapamil and nicardipine. It can be concluded that endothelin-1 is a vasoconstrictor in the human umbilical artery, probably acting via more than one contraction-mediating receptor. The I-125-endothelin-1 binding sites demonstrated in the smooth muscle la yer of the vessel may correspond to receptors mediating the contractil e effect. The mechanisms of action seems to involve activation of Ca2 channels. The present study does not give any evidence for interactio n of endothelin-1 with other endothelium-derived vasoactive agents in this vessel.