Specific hepatocyte endothelin receptors and the direct effect of endothelin on protein synthesis

High affinity binding sites for endothelin (ET)-1 were identified on mouse parenchymal hepatocytes. The binding of 125I-ET-1 at its site was specific, saturable, and time dependent, but dissociation of the receptor-bound ligand was minimal. Scatchard analysis of the binding data revealed the presence of a non-interacting, single class of high-affinity binding sites on hepatocytes. The dissociation binding constant (Kd) and the maximal binding capacity (Bmax) were determined as 2.1 x 10(-10) M and 3.0 x 10(2) sites/cell, respectively. Unlabeled ET-1 competitively inhibited the binding of 125I-ET-1 to primary cultured mouse hepatocytes with a concentration for half-maximal inhibition (IC50) of 2.0 x 10(-10) M. ET-1 apparently enhanced total protein synthesis in primary cultured mouse hepatocytes concentration ranging from 3 x 10(-11) M to 3 x 10(-8) M in a dose-dependent manner. These data indicate that specific receptor for ET-1 is present in the mouse liver and suggest for the first time that hepatocyte protein synthesis is involved in its direct, agonistic effect.