Characterization of endothelin receptors and localization of 125I-endothelin-1 binding sites in human umbilical artery.
The mechanisms of endothelin-1-induced contractile response in the human umbilical artery were investigated in vitro. Autoradiography revealed 125I-endothelin-1 binding sites in the smooth muscle layer of the vessel wall. Endothelin-1 and sarafotoxin S6b induced concentration-dependent contractions while endothelin-3 was virtually without contractile effect. The endothelin ETA receptor antagonist BQ 123 did not affect the contraction to endothelin-1 but antagonized the contraction to 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 125I-endothelin-1 binding sites demonstrated in the smooth muscle layer of the vessel may correspond to receptors mediating the contractile effect. The mechanisms of action seems to involve activation of Ca2+ channels. The present study does not give any evidence for interaction of endothelin-1 with other endothelium-derived vasoactive agents in this vessel.
Bodelsson
G
G
Department of Obstetrics and Gynecology at Malmö, University of Lund, General Hospital, Sweden.
Stjernquist
M
M
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000378:metabolism*; D014469:Umbilical Arteries / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology; D019323:omega-N-Methylarginine
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D019323:omega-N-Methylarginine; D001120:Arginine; D014700:Verapamil; D009529:Nicardipine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)