Bax W A, Bruinvels A T, van Suylen R J, Saxena P R, Hoyer D
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Oct;348(4):403-10. doi: 10.1007/BF00171340.
In the present experiments we investigated endothelin (ET) receptors in the human coronary artery, and in ventricular and atrial muscle using quantitative receptor autoradiography. Displacement of [125I]Sf6b (Sarafotoxin S6b) (30 pM)- and [125I]ET-1 (30 pM)-labeled binding sites was studied using ET-1, the ETA receptor selective ligand BQ-123 (cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp-]), and the ETB receptor selective ligand [Ala1, 3, 11, 15]ET-1. Specific binding was more dense in atrium and coronary artery (relative optical density (r.o.d.): 0.14 +/- 0.01 and 0.16 +/- 0.01, respectively) than in ventricular muscle (r.o.d.: 0.10 +/- 0.01). In the coronary artery, binding was especially dense in the media. ET-1 displaced [125I]ET-1 and [125I]Sf6b monophasically in atrium, ventricle and coronary artery. [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1 and [125I]Sf6b-labeled sites biphasically in the ventricle and in the atrium. In the human coronary artery, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1-labeled sites monophasically (pIC50: ET-1 (9.72 +/- 0.12) > BQ-123 (6.84 +/- 0.08) > [Ala1,3,11,15]ET-1 (6.40 +/- 0.12). In contrast, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]Sf6b-labeled coronary artery sites biphasically (high affinity pIC50: BQ-123, 9.03 +/- 0.25; [Ala1,3,11,15]ET-1, 8.40 +/- 0.14; low affinity pIC50: BQ-123, 7.24 +/- 0.14; [Ala1,3,11,15]ET-1, 6.99 +/- 0.09). These data indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
在当前实验中，我们使用定量受体放射自显影技术研究了人冠状动脉以及心室肌和心房肌中的内皮素（ET）受体。使用ET-1、ETA受体选择性配体BQ-123（环[D-天冬氨酸-L-脯氨酸-D-缬氨酸-L-亮氨酸-D-色氨酸-]）和ETB受体选择性配体[Ala1,3,11,15]ET-1研究了[125I]Sf6b（沙拉毒素S6b）（30 pM）和[125I]ET-1（30 pM）标记的结合位点的置换情况。特异性结合在心房和冠状动脉中（相对光密度（r.o.d.）：分别为0.14±0.01和0.16±0.01）比在心室肌中（r.o.d.：0.10±0.01）更密集。在冠状动脉中，结合在中膜特别密集。ET-1在心房、心室和冠状动脉中单相置换[125I]ET-1和[125I]Sf6b。[Ala1,3,11,15]ET-1和BQ-123在心室和心房中双相置换[125I]ET-1和[125I]Sf6b标记的位点。在人冠状动脉中，[Ala1,3,11,15]ET-1和BQ-123单相置换[125I]ET-1标记的位点（半数抑制浓度的负对数（pIC50）：ET-1（9.72±0.12）>BQ-123（6.84±0.08）>[Ala1,3,11,15]ET-1（6.40±0.12）。相比之下，[Ala1,3,11,15]ET-1和BQ-123双相置换[125I]Sf6b标记的冠状动脉位点（高亲和力pIC50：BQ-123，9.03±0.25；[Ala1,3,11,15]ET-1，8.40±0.14；低亲和力pIC50：BQ-123，7.24±0.14；[Ala1,3,11,15]ET-1，6.99±0.09）。这些数据表明，在人心室肌和心房肌中，[125I]ET-1和[125I] Sf6b标记的ETA和ETB结合位点均存在。（摘要截短于250字）
