Detection of endothelin receptors in human coronary artery vascular smooth muscle cells but not endothelial cells by using electron microscope autoradiography.
Endothelin A (ET(A)) and ET(B) receptors located on vascular smooth-muscle cells mediate potent vasoconstriction in animal and human blood vessels. Although vascular endothelial ET(B) receptors mediate vasodilatation through release of nitric oxide, prostacyclin, or an endothelium-derived hyperpolarizing factor in animal vessels, there is less evidence to support ET-mediated endothelium-dependent relaxation in human arteries. We investigated the regional and subcellular localization of ET-receptor subtypes in human epicardial coronary arteries obtained from patients with congestive heart failure undergoing cardiac transplantation. Radioligand-binding studies revealed a predominance of the ET(A)-receptor subtype in the coronary artery. ET(A) and ET(B) receptors were located in the media and in perivascular structures by using macroautoradiography. Specific binding in the intimal layer was low. Autoradiography at the ultrastructural level revealed the presence of ET(A) and ET(B) receptors on medial vascular smooth-muscle cell plasmalemma and plasmalemmal vesicles with a predominance of the ET(A) subtype. ET receptors were not detected in either luminal endothelial cells of the coronary arteries or endothelial cells lining small adventitial blood vessels. This study is the first to identify the subcellular localization of ET receptors in human coronary artery vascular smooth-muscle cells. These receptors probably mediate the well-established vasoconstrictor response to ET-1. The inability to detect ET receptors on endothelial cells suggests a minor role for endothelial cells in ET-mediated vasodilatation of the coronary vasculature.
Russell
F D
FD
Clinical Pharmacology Unit, Addenbrooke's Hospital, University of Cambridge, England.
Skepper
J N
JN
Davenport
A P
AP
D000328:Adult; D001345:Autoradiography; D001381:Azepines / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D003331:Coronary Vessels / Q000648:ultrastructure*; D065128:Endothelin Receptor Antagonists; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000648:ultrastructure*; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000648:ultrastructure*
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D007211:Indoles; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C079574:FR 139317