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.
Suzaki
S
S
Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, Japan.
Suzaki
A
A
Yamamoto
Y
Y
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D014176:Protein Biosynthesis; D017466:Receptors, Endothelin / Q000378:metabolism*
D016232:Endothelins; D017466:Receptors, Endothelin