[3H]bosentan binding to human coronary artery: functional correlates.
The binding characteristics and localization of bosentan, an orally active endothelin-1 (ET-1) antagonist, were studied on sections of human coronary artery by in vitro autoradiography. Competition studies were performed to determine the ability of bosentan to prevent [125I]ET-1 binding to the coronary vasculature. The effects of bosentan on ET-1-induced contraction of the coronary artery were also studied in vitro. [3H]Bosentan bound to the tunica media of the human coronary artery. Unlabeled bosentan prevented [125I]ET-1 binding to this vessel in a concentration-dependent manner, and functional studies indicated that bosentan antagonizes ET-1--induced constriction. These data show that bosentan is able to reduce ET-1 binding to the human coronary artery and ET-1 constrictor effects in vitro. Bosentan is an orally active ET-1 antagonist, and these results suggest that this compound might be used to block the effects of locally released ET-1 in pathologic conditions, such as atherosclerosis, angina, and myocardial ischemia.
Dashwood
M R
MR
Department of Physiology, Royal Free Hospital School of Medicine, London, England.
Timm
M
M
Muddle
J R
JR
Shah
D
D
Tippins
J R
JR
Kaski
J C
JC
D001345:Autoradiography; D000077300:Bosentan; D003331:Coronary Vessels / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism*; D006801:Humans; D013449:Sulfonamides / Q000378:metabolism*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D000077300:Bosentan