The selective endothelin ETA receptor antagonist BQ123 antagonizes endothelin-1-mediated mitogenesis.
The mitogenic effects of endothelin isopeptides and the selective ETA receptor antagonist BQ123 were evaluated in rat aortic vascular smooth muscle cells. Endothelin-1 (ET-1) and endothelin-3 (ET-3) produced concentration-dependent increases in [3H]thymidine incorporation (EC50 = 0.1 and 25 nM, respectively). The ETB-selective agonist sarafotoxin 6c did not produce significant effects on [3H]thymidine incorporation. BQ123 produced selective and concentration-dependent inhibition of ET-1-mediated [3H]thymidine incorporation. These data demonstrate that ET-1-mediated mitogenesis in vascular smooth muscle is mediated by ETA receptors.
Ohlstein
E H
EH
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Arleth
A
A
Bryan
H
H
Elliott
J D
JD
Sung
C P
CP
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D008297:Male; D008938:Mitosis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000187:drug effects; D017466:Receptors, Endothelin; D013936:Thymidine / Q000378:metabolism
D016232:Endothelins; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D004247:DNA; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D013936:Thymidine