ENDOTHELIN RECEPTORS IN THE HUMAN CORONARY-ARTERY, VENTRICLE AND ATRIUM - A QUANTITATIVE AUTORADIOGRAPHIC ANALYSIS

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 [I-125]Sf6b (Sarafotoxin S6b) (30 pM)- and [I-125]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 (ro.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 [I-125I]ET-1 and [I-125]Sf6b monophasically in atrium, ventricle and coronary artery. [Ala1,3,11,15]ET-1 and BQ-123 displaced [I-125]ET-1 and [I-125]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 [I-125]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 [I-125]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 [I-125]ET-1 and [I-125] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle. In the human coronary artery, both radioligands labeled ETA binding sites, but [I-125] Sf6b also labeled a non-ETA, non-ETB binding site with relatively high affinity for both BQ-123 and [Ala1,3,11,15] ET-1.