title: The selective endothelin ETA receptor antagonist BQ123 antagonizes endothelin-1-mediated mitogenesis.
abstract: 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.
authors.affiliation: Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
authors.forename: E H
authors.initials: EH
authors.lastname: Ohlstein
authors.forename: A
authors.initials: A
authors.lastname: Arleth
authors.forename: H
authors.initials: H
authors.lastname: Bryan
authors.forename: J D
authors.initials: JD
authors.lastname: Elliott
authors.forename: C P
authors.initials: CP
authors.lastname: Sung
mesh_terms: 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
chemical_list: D016232:Endothelins; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D004247:DNA; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D013936:Thymidine