Specific receptor for endothelin in cultured rat cardiocytes

Specific binding sites for the endothelium-derived vasoconstrictor endothelin (ET) and its effect on cytosolic free Ca 2+ concentrations ([Ca 2+] i) were studied in a primary culture of cardiocytes from neonatal rats. Binding studies using 125I-labeled-porcine ET as a radioligand revealed the presence of a single class of high-affinity binding sites for ET in cardiocytes with an apparent K d of 6−9×10 −10 M and a B max of 50,000–80,000 sites/cell. Neither various vasoconstrictors nor Ca 2+-channel blockers affected the binding. Pretreatment with ET substantially reduced the total number of ET receptors without changing their affinity. ET dose- dependently increased [Ca 2+] i in fura-2-loaded cardiocytes. These data indicate that cardiocytes have specific ET receptors that are controlled by a down-regulation mechanism, and that ET induces a receptor-mediated increase in [Ca 2+] i in cardiocytes.