Mechanisms of action of endothelin-1 in rat adrenal.
Displacement curves of 125I-Endothelim-1 (ET-1) binding to rat adrenal cells with unlabeled ET-1, and the ET-1 receptor-related peptides sarafotoxin and BQ-123, show that rat adrenal cortex possess, as its bovine counterpart, two different receptors to ET-1 named ET-A and ET-B. Binding of ET-1 to its rat adrenal receptors stimulates i) aldosterone production, in vivo and in vitro ii) calcium influx, which is mediated through voltage dependent- and receptor operated- calcium channels, iii) cholesterol uptake, iv) stimulation of Na+/K+-ATPase and iv) diacylglycerol production. While the last effect is mediated through ET-A receptors the others involve binding of ET-1 to ET-B receptors. Finally, ouabain potentiates the ET-1-mediated stimulation of aldosterone production, suggesting that the effect of the peptidic hormone on Na+/K+-ATPase could act as a negative feedback mechanism.
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and PRHOM-CONICET, Argentina.
A
A
Pecci
D G
DG
Romero
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CP
Lantos
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EN
Cozza
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004075:Diglycerides / Q000096:biosynthesis; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D014757:Viper Venoms / Q000378:metabolism / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
C011439:1,2-diacylglycerol; D015220:Calcium Channels; D004075:Diglycerides; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; D000450:Aldosterone; D010042:Ouabain; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002784:Cholesterol; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium