ENDOTHELIN ACTION IN RAT-LIVER - RECEPTORS, FREE CA2+ OSCILLATIONS, AND ACTIVATION OF GLYCOGENOLYSIS

High affinity binding sites for endothelin (ET) were identified on rat liver plasma membranes. Binding of I-125-ET-1 with its site was specific, saturable, and time dependent (kappa(obs) = 0.019 +/- 0.001 min-1), but dissociation of receptor-bound ligand was minimal. A single class of high affinity binding sites for I-125-ET-1 was identified with potency of related peptides was similar to that in binding experiments (ET-1 > ET-3 > big ET-1). These data constitute the first demonstration of the presence of ET-1 binding sites in liver which is associated with a rise in cytosolic free Ca2+ and a potent glycogenolytic effect. We conclude that ET-1 behaves as a typical Ca2+ mobilizing hormone in liver. series of repetitive, sustained Ca2+ transients. ET-1 had no effect on cAMP production. Finally, Et-1 caused a rapid and sustained stimulation of glycogenolysis in rat hepatocytes. A 1.8-fold maximal increase in glycogen phosphorylase a was observed at 1 pM ET-1, with an EC50 of 0.03 pM. Stimulation of the enzyme was specific for ET-1 since the order of experiments (ET-1 > ET-3 > big ET-1). These data constitute the first demonstration of the presence of ET-1 binding sites in liver which is associated with a rise in cytosolic free Ca2+ and a potent glycogenolytic effect. We conclude that ET-1 behaves as a typical Ca2+ mobilizing hormone in liver.