Uses
BMS 182874 hydrochloride is an orallyactive, highly selective endothelin receptor (ETA receptor) antagonist, with IC50 value of 0.150 μM, Ki of 0.055 μM. BMS 182874 hydrochloride reduces the arterial pressure of Deoxycorticosterone acetate (HY-B1472) induced hypertension model in rats, and can be used for cardiovascular disease research[1].
Biological Activity
ki: 61 nm for eta in vsm-a10 cells; 48 nm for eta in cho cellsendothelin (et) was originally identified as a potent vasoactive substance secreted by endothelial cells that stimulated force development in isolated pig coronary arteries. et-1 belongs to a family of highly conserved 21-amino-acid peptides produced in numerous tissues including the lung, kidney, eye, gut and central nervous system. bms-182874 is a low molecular weight, nonpeptide endothelin (el) receptor antagonist.
in vitro
bms-182874 competitively inhibited the binding of [125i]et-1 to eta receptors in rat vascular smooth muscle a10 (vsm-a10) cell membranes (ki = 61 nm) and in cho cells stably expressing the human eta receptor (ki = 48 nm), but was a weak inhibitor at etb receptors (ki > 50 μm) and non-et receptors. bms-l 82874 inhibited et-l -stimulated inositol phosphate accumulation (kb 75 nm) and calcium mobilization (ki = 140 nm) without suppressing the maximal responses in vsm-a10 cells [1].
in vivo
when administered either orally (ed50 = 30 μmol/kg) or intravenously (ed50 = 24 μmol/kg) to conscious, normotensive rats, bms-182874 blunted the pressor response to exogenous et-l . these data demonstrate that bms-l 82874 is a competitive, selective and orally active eta receptor antagonist [1].
References
[1] maria l webb, j. eileen bird, eddie c. k. liu, patricia m. rose, randy serafino, philip d. stein and suzanne moreland. bms-182874 is a selective, nonpeptide endothelin eta receptor antagonist. jpet 272:1124-1134, 1995.
