Endothelin-1 as an autocrine growth factor for endothelial cells.
To elucidate the role of endothelin-1 (ET-1) as an autocrine growth factor for vascular endothelial cells (ECs), we studied the effects of phosphoramidon, an inhibitor of ET-1-converting enzyme, on the production of ET-1-like immunoreactivity (LI), [125I]ET-1 binding activity, ETB receptor mRNA expression, phosphoinositide breakdown, and DNA synthesis in cultured bovine carotid artery ECs. Phosphoramidon dose-dependently decreased ET-1-LI production but reciprocally increased [125I]ET-1 binding capacity. ET-1 and ET-3 equipotently inhibited the binding of [125I]ET-1 only in the presence of phosphoramidon. Northern blot analysis revealed that ETB receptor mRNA expression was more evident in phosphoramidon-treated cells than in nontreated cells. In the presence of phosphoramidon, ET-1 and ET-3 equipotently stimulated inositol 1,4,5-trisphosphate formation and [3H]-thymidine incorporation into cultured ECs. Both phosphoramidon and anti-ET-1 antibody inhibited basal [3H]thymidine incorporation. These data suggest that endogenous ET-1 constitutively secreted by ECs is an autocrine growth factor via ETB receptors.
Eguchi
S
S
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Hirata
Y
Y
Imai
T
T
Marumo
F
F
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D016232:Endothelins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006020:Glycopeptides / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology*; D017466:Receptors, Endothelin / Q000502:physiology
D016232:Endothelins; D006020:Glycopeptides; D006133:Growth Substances; D017466:Receptors, Endothelin; D004247:DNA; C008890:phosphoramidon