A novel ETA antagonist (BQ‐123) inhibits endothelin‐1‐induced phosphoinositide breakdown and DNA synthesis in rat vascular smooth muscle cells

FEBS Letters

Yano, Mitsuo¹  Eguchi, Satoru²  Hirata, Yukio²  Marumo, Fumiaki²  Ihara, Masaki¹ 

[1] Central Research Laboratories, Banyu Pharmaceutical Co., 2-9-3 Shimomeguro, Meguroku, Tokyo 153, Japan;Second Department of Internal Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo 113, Japan

关键词: Endothelin-1;    Receptor antagonist;    Inositol trisphosphate;    DNA synthesis;    Vascular smooth muscle cell;   

DOI  :  10.1016/0014-5793(92)80451-L

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effects of a novel cyclic pentapeptide (BQ-123), an endothelin (ET) antagonist selective for the ET_A 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 K _i of 4 × 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 ET_A receptor subtype.

【 授权许可】

Unknown