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.
