Inositol phosphate release and steroidogenesis in rat adrenal glomerulosa cells. Comparison of the effects of endothelin, angiotensin II and vasopressin

Abstract

Endothelin has steroidogenic activity in adrenal glomerulosa cells, as do two other vasoconstrictor peptides, angiotensin II and vasopressin. The steroidogenic activities of angiotensin II and vasopressin are probably mediated via the phosphatidylinositol-turnover pathway and associated changes in cytosolic Ca2+ concentration. Endothelin caused a steroidogenic response, which was small compared with that to angiotensin II and quantitatively similar to the vasopressin response. Cytosolic free Ca2+ responses were similarly higher to angiotensin II than to either of the other two peptides. However, total inositol phosphate responses to endothelin and angiotensin II were similar when these were measured over 20 min, and were quantitatively greater than the vasopressin response. A detailed study has been made of the phosphatidylinositol-turnover response to endothelin in comparison with responses to angiotensin II and vasopressin. Each of the three peptides produced a rapid and transient rise in Ins(1,4,5)P3 (max. 5-15 s), followed by a slow sustained rise. Ins(1,4,5)P3 was metabolized by both dephosphorylation and phosphorylation pathways, but the relative importance of the two metabolic pathways was different under stimulation by each of the three peptides. These findings show that adrenal glomerulosa cells can distinguish between the stimulation of phosphatidylinositol turnover by three different effectors. These differences in the pathway may be associated with the observed different steroidogenic and Ca2+ responses to the three peptides.

Regulation of Blood Pressure and Salt Homeostasis by Endothelin

“…7) (17, 126, 290, 479, 567, 611, 814). This stimulatory effect of ET peptides is relatively small compared with that of ANG II, based on studies in which ET-1 was systemically administered in vivo (480), in dispersed rat zona glomerulosa cells (478, 836), or using human adrenal slices (875). In addition, ET-1 may potentiate ANG II actions in the adrenal.…”

“…In rat adrenal glomerulosa cells, ET-1 increased [Ca 2+ ] i (836). ET B activation increased [Ca 2+ ] i in rat zona glomerulosa cells, at least in part, through intracellular release; the response was independent of dihydropyridine-sensitive Ca 2+ channels (19).…”

“…In frog adrenal explants, ET-1 increased IP 3 via ET A (84). In rat adrenal glomerulosa cells, ET-1 increased IP levels (836). In dispersed human zona glomerulosa cells, ET A and ET B activation increases IP 3 (17).…”

Endothelin Signaling Pathways in Rat Adrenal Medulla

“…It has been shown that ET is able to stimulate PI turnover in rat adrenal cortex (Woodcock et al, 1990) and adrenal medulla (Garrido and Israel, 1997). Furthermore, phosphoinositide (PI) turnover induced by the activation of ET receptors, is involved with the catecholamines secretagogue activity elicited by ET-related peptides (Belloni et al, 1997).…”

Role of phospholipases in adrenal steroidogenesis

“…For example, carbachol (a stable acetylcholine receptor agonist), endothelin-1, sphingosine 1-phosphate, and vasopressin have all been reported to activate phosphoinositide hydrolysis to stimulate adrenocortical cell steroid hormone production (Kojima et al 1986, Woodcock et al 1986, Woodcock et al 1990, Bollag et al 1992, Andreis et al 2001, Delarue et al 2004, Brizuela et al 2006. Neuropeptide B has also been shown to increase IP 3 levels in adrenal fasciculata/ reticularis cells, and the PLC inhibitor U73122 reduced neuropeptide-elicited cortisol production (Mazzocchi et al 2005).…”