The effect of the ETA receptor antagonist, FR 139317, on [125I]-ET-1 binding to the atherosclerotic human coronary artery.
1. The distribution of [125I]-endothelin (ET-1) binding sites on atherosclerotic human epicardial coronary arteries has been studied by in vitro receptor autoradiography. 2. [125I]-ET-1 binding was to the tunica media and regions of neovascularization. 3. Competition studies were carried out in the presence of ET-1 and the ETA receptor antagonist, FR 139317. The IC50 values for ET-1 at the tunica media and regions of neovascularization were similar (mean +/- s.e.mean of n = 4 patients, 2.5 +/- 0.9 nM and 2.9 +/- 0.9 nM, respectively) whereas IC50 values for FR 139317 at regions of neovascularization (607 +/- 34 nM) were significantly higher than those of the tunica media (12.6 +/- 2.4 nM) (P < 0.0001). 4. These results indicate that ETA receptors are present on the tunica media of the diseased human coronary artery whereas a different ET receptor subtype exists at regions of neovascularization.
Dashwood
M R
MR
Department of Physiology, Royal Free Hospital School of Medicine, London.
Allen
S P
SP
Luu
T N
TN
Muddle
J R
JR
D001345:Autoradiography; D001381:Azepines / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism*; D016027:Heart Transplantation; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000473:pathology
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D007457:Iodine Radioisotopes; C079574:FR 139317