Endothelin binding to cultured calf adrenal zona glomerulosa cells and stimulation of aldosterone secretion.
Endothelins are a group of potent vasoconstrictors whose structure was deduced from genomic DNA. ET-1 was first isolated from culture supernatants from porcine endothelial cells and ET-3 was identified from a rat DNA library. We report on the binding of 125I-ET-1 to zona glomerulosa cells in culture and on its ability to stimulate aldosterone secretion. Cultured calf adrenal zona glomerulosa cells have saturable, high affinity [Kd = 1.00 +/- 0.17 X 10(-10) M (SEM)] receptors which bind ET-1 in a temperature and time dependent manner. Binding was specific and angiotensin II, vasopressin, ANP, BNP, apamin, calcium channel agonists or antagonists did not interact with the receptor. ET-3 displaced 125I-ET-1 from the receptor with a relative potency of 0.39 +/- 0.1% (SEM) that of ET-1. ET-1 incubated with cultured glomerulosa cells stimulated aldosterone secretion in a dose dependent manner but it was less potent than angiotensin II. ET-3 had less than 1% the relative potency of ET-1 stimulating aldosterone secretion. This data suggest that ET-1 is an independent stimulator of aldosterone secretion and we are speculating that it might be important in those situations, like in malignant hypertension, where endothelial damage might result in increased ET-1 production.
Cozza
E N
EN
Department of Internal Medicine, University of South Florida College of Medicine, Tampa 33612.
Gomez-Sanchez
C E
CE
Foecking
M F
MF
Chiou
S
S
D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D016232:Endothelins; D007700:Kinetics; D010455:Peptides / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000378:metabolism* / Q000502:physiology; D015384:Zona Glomerulosa / Q000378:metabolism*
D016232:Endothelins; D010455:Peptides; D011956:Receptors, Cell Surface; D014662:Vasoconstrictor Agents; D000450:Aldosterone