The selective endothelin ETA receptor antagonist BQ123 antagonizes endothelin-1-mediated mitogenesis

E H Ohlstein; A Arleth; H Bryan; J D Elliott; C P Sung

doi:10.1016/0922-4106(92)90109-9

The selective endothelin ETA receptor antagonist BQ123 antagonizes endothelin-1-mediated mitogenesis

Eur J Pharmacol. 1992 Apr 10;225(4):347-50. doi: 10.1016/0922-4106(92)90109-9.

Authors

E H Ohlstein¹, A Arleth, H Bryan, J D Elliott, C P Sung

Affiliation

¹ Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.

PMID: 1323478
DOI: 10.1016/0922-4106(92)90109-9

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.

MeSH terms

Animals
Cells, Cultured
DNA / biosynthesis
Dose-Response Relationship, Drug
Endothelins / pharmacology*
Male
Mitosis
Muscle, Smooth, Vascular / cytology
Muscle, Smooth, Vascular / drug effects*
Muscle, Smooth, Vascular / metabolism
Peptides, Cyclic / pharmacology*
Rats
Rats, Inbred Strains
Receptors, Cell Surface / antagonists & inhibitors*
Receptors, Cell Surface / drug effects
Receptors, Endothelin
Thymidine / metabolism

Substances

Endothelins
Peptides, Cyclic
Receptors, Cell Surface
Receptors, Endothelin
DNA
cyclo(Trp-Asp-Pro-Val-Leu)
Thymidine