Characterization of endothelin-1 receptor subtypes in isolated human cardiomyocytes

On cardiac membranes and isolated cardiomyocytes from the human heart, cell -type distribution and functional activities of endothelin-1 (ET-1) recepto r subtypes were investigated by using binding methods and messenger RNA (mR NA) in situ hybridization. The ET-receptor antagonist EMS-182874 selectivel y and competitively inhibits ETA receptors both on isolated myocytes and ve ntricular membranes with similar to 1,300 times greater affinity for ETA th an ETB subtypes. The [I-125]-ET-1 specific binding revealed 42,851 +/- 2,54 6 receptors/ myocyte with a prevalent proportion of ETA-receptor subtypes o n both myocytes (84 +/- 2%) and ventricular membranes (66 +/- 3%). In situ hybridization studies revealed that mRNA for ETA receptors was expressed on both myocytes and nonmyocyte cells, whereas mRNA for ETB receptors was alm ost exclusively expressed on fibroblasts and endothelial cells. Specific bi nding of [I-125]-ET-1 to both myocytes and ventricular membranes in the pre sence of specific ETA (BMS-182874) and ETB (BQ-788)-receptor antagonists sh owed a displacement of [I-125]-ET-1 by unlabeled ET-1, which were significa ntly faster from ETB than from ETA. This suggests a clearance function of v entricular ETB receptors.