A novel ETA antagonist (BQ-123) inhibits endothelin-1-induced phosphoinositide breakdown and DNA synthesis in rat vascular smooth muscle cells.
The effects of a novel cyclic pentapeptide (BQ-123), an endothelin (ET) antagonist selective for the ETA receptor subtype, on phosphoinositide breakdown and DNA synthesis stimulated by ET-1 were studied in cultured rat vascular smooth muscle cells (VSMC). BQ-123 competitively inhibited the binding of [125I]ET-1 to VSMC with the apparent Ki of 4 x 10(-9) M. BQ-123 dose-dependently inhibited formation of inositol-1,4,5-trisphosphate and [3H]thymidine uptake stimulated by ET-1. These data suggest that the ET-1-induced DNA synthesis in VSMC is mainly mediated by ETA receptor subtype.
Eguchi
S
S
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Hirata
Y
Y
Ihara
M
M
Yano
M
M
Marumo
F
F
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D017466:Receptors, Endothelin
D016232:Endothelins; D010456:Peptides, Cyclic; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D004247:DNA; C072247:cyclo(Trp-Asp-Pro-Val-Leu)