title: Action of endothelins on hepatic stellate cells.
abstract: To elucidate the role played by hepatic sinusoidal cells in the regulation of the circulatory status in the liver, the effect of endothelins (ETs) on primary-cultured stellate cells was examined. Kinetic analysis with 125I-labeled ET-1 revealed that stellate cells have ET receptors with a Kd value of 141 pM and a Bmax of 12.3 fmol/10(5) cells. ET-1, -2, and -3 dose-dependently increased inositol monophosphate (InsP) levels in stellate cells with an EC50 of 0.53, 1.63, and 1.88nM, respectively. Binding of 125I-labeled ET-1 to stellate cells and the ET-enhanced InsP formation were suppressed by preincubating the cells with 10 nM of unlabeled ET-1 or ET-3 for more than 3 h, indicating down-regulation and desensitization of ET receptors by homologous ligands. Binding of ETs to surface receptors induced a marked contraction of stellate cells. Stellate cells rapidly reacted to ETs, as detected by the flexible silicone-rubber-membrane method; 78%, 73%, and 58% of the stellate cells contracted 2.5 min after the addition of 10 nM of ET-1, ET-2, or ET-3, respectively. On the other hand, ETs also triggered a long-lasting contraction of the cells, as revealed with hydrated collagen gels. The ET-induced contraction of stellate cells decreased the diameter of the collagen lattice by about 60%, and this action was inhibited either by cytochalasin B or by H-7, a protein kinase C inhibitor. These and other results suggest that ETs induced cell contraction by some mechanism that involved protein kinase C.
authors.affiliation: Third Department of Internal Medicine, Osaka City University Medical School, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kawada
authors.forename: T
authors.initials: T
authors.lastname: Kuroki
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: K
authors.initials: K
authors.lastname: Kaneda
authors.forename: K
authors.initials: K
authors.lastname: Decker
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D007457:Iodine Radioisotopes; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D016232:Endothelins; D007295:Inositol Phosphates; D007457:Iodine Radioisotopes; D017466:Receptors, Endothelin; D000242:Cyclic AMP; D006152:Cyclic GMP