Endothelins stimulate aldosterone secretion from dispersed rat adrenal zona glomerulosa cells, acting through ETB receptors coupled with the phospholipase C-dependent signaling pathway.
Compelling evidence indicates that endothelins (ETs) stimulates aldosterone secretion from rat zona glomerulosa (ZG) cells, acting through the ETB receptor subtype. We have investigated the mechanisms transducing the aldosterone secretagogue signal elicited by the pure activation of ETB receptors. Aldosterone response of dispersed rat ZG cells to the selective ETB-receptor agonist BQ-3020 was not affected by inhibitors of adenylate cyclase/protein kinase (PK)A, tyrosine kinase-, mitogen-activated PK-, cyclooxygenase- and lipoxygenase-dependent pathways. In contrast, the inhibitor of phospholipase C (PLC) U-73122 abrogated, and the inhibitors of PKC, phosphatidylinositol trisphosphate (IP(3))-kinase and calmodulin (calphostin-C, wortmannin and W-7, respectively) partially prevented aldosterone response to BQ-3020. When added together, calphostin-C and wortmannin or W-7 abolished the secretagogue effect of BQ-3020. BQ-3020 elicited a marked increase in the intracellular Ca2+ concentration ([Ca2+]i) in dispersed rat ZG cells, and the effect was abolished by the Ca(2+)-release inhibitor dantrolene. The Ca2+ channel blocker nifedipine affected neither aldosterone nor Ca2+ response to BQ-3020. Collectively, our findings suggest that (1) ETs stimulate aldosterone secretion from rat ZG cells through the activation of PLC-coupled ETB receptors; (2) PLC stimulation leads to the activation of PKC and to the rise in [Ca2+]i with the ensuing activation of calmodulin; and (3) the increase in [Ca2+] is exclusively dependent on the stimulation of IP(3)-dependent Ca2+ release from intracellular stores.
Andreis
P G
PG
Department of Human Anatomy and Physiology (Section of Anatomy), University of Padua, Via Gabelli 65, I-35121, Padua, Italy.
Tortorella
C
C
Malendowicz
L K
LK
Nussdorfer
G G
GG
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism; D015384:Zona Glomerulosa / Q000378:metabolism*
D016232:Endothelins; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D000450:Aldosterone; D010738:Type C Phospholipases