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Endothelin-1 as an autocrine growth factor for endothelial cells.

Authors :
Eguchi S
Hirata Y
Imai T
Marumo F
Source :
Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 1995; Vol. 26 Suppl 3, pp. S279-83.
Publication Year :
1995

Abstract

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.

Details

Language :
English
ISSN :
0160-2446
Volume :
26 Suppl 3
Database :
MEDLINE
Journal :
Journal of cardiovascular pharmacology
Publication Type :
Academic Journal
Accession number :
8587388