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

Abstract
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 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 ETA receptor subtype.