Endothelin receptors in the human coronary artery, ventricle and atrium

Abstract

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 ET_A receptor selective ligand BQ-123 (cyclo[D-Asp-L-Pro-D Val-L-Leu-D-Trp-]), and the ETB receptor selective ligand [Ala^1,3,11,15]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. [Ala^1,3,11,15]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, [Ala^1,3,11,15]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) > [Ala^1,3,11,15]ET-1 (6.40±0.12). In contrast, [Ala^1,3,11,15]ET-1 and BQ-123 displaced [¹²⁵I] Sf6b-labeled coronary artery sites biphasically (high affinity pIC₅₀: BQ-123, 9.03±0.25;[Ala^1,3,11,15]ET-1, 8.40±0.14; low affinity pIC₅₀: BQ-123, 7.24±0.14; [Ala^1,3,11,15]ET-1, 6.99±0.09). These data indicate that both [¹²⁵I]ET-1 and [¹²⁵I] Sf6b-labeled ET_A and ET_B binding sites in human ventricular and atrial muscle. In the human coronary artery, both radioligands labeled ET_A binding sites, but [¹²⁵I] Sf6b also labeled a non-ET_A, non-ET_B binding site with relatively high affinity for both BQ-123 and [Ala^1,3,11,15] ET-1.