Endothelin-1 suppression of rat adipocyte precursor cell differentiation in serum-free culture.
The effect of endothelin-1 (ET-1) on differentiation of rat adipocyte precursor cells in serum-free culture and of the adipogenic fibroblast cell line TA1 was studied. ET-1 inhibited differentiation of rat adipocyte precursor cells into adipocytes in a dose-dependent fashion, while the peptide exerted no effect on TA1 cells. Rat adipose precursor cells possessed a single class of high affinity ET-1 receptor with a Kd of 0.71 nM and a binding capacity of 47,000 sites/cell. Affinity cross-linking of [125I]ET-1 showed two bands with molecular masses of 86 and 50 kilodaltons in rat adipose precursor cells and a single broad band with a molecular mass of 55-60 kilodaltons in TA1 cells. Pertussis toxin and the protein kinase-C inhibitors, H-7 and staurosporine, all of which enhanced adipocyte differentiation of rat adipose precursor cells, partially reversed ET-1 inhibition. These results showed the divergent effect of ET-1 on adipocyte conversion and indicated the possible involvement of a pertussis toxin-sensitive pathway and protein kinase-C at least in part in the inhibitory action of ET-1 on adipocyte differentiation.
Shinohara
O
O
Department of Pediatrics, Tokai University School of Medicine, Kanagawa-ken, Japan.
Murata
Y
Y
Shimizu
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D017466:Receptors, Endothelin; D019311:Staurosporine; D013234:Stem Cells / Q000187:drug effects*
D000470:Alkaloids; D016232:Endothelins; D007546:Isoquinolines; D010879:Piperazines; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019204:GTP-Binding Proteins; D019311:Staurosporine