Effects of Angiotensin II, K+, Adrenocorticotropin, Serotonin, Adenosine 3′,5′-Monophosphate, Guanosine 3′,5′-Monophosphate, A23187, and EGTA on Aldosterone Synthesis and Phospholipid Metabolism in the Rat Adrenal Zona Glomerulosa*

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Abstract
Rat adrenal glomerulosa cells and capsules were incubated in vitro with angiotensin II (A-II), ACTH, K+, (Bu)2cAMP, (Bu)2cGMP, A23187 [calcimycin], and serotonin to compare their effects on steroidogenesis and phospholipid metabolism. In both glomerulosa cells and capsules, A-II, ACTH, K+, (Bu)2cAMP, and serotonin enhanced aldosterone or corticosterone production, but only A-II, K+, and serotonin significantly and consistently increased the incorporation of [32P]Pi into phosphatidic acid (PA) and phosphatidylinositol (PI). A-II, ACTH, K+, (Bu)2cAMP, and serotonin all provoked nearly 2-fold increases in PI mass in adrenal capsules. (Bu)2cGMP had relatively small effects, if any, on aldosterone production or glomerulosa phospholipid metabolism. In adrenal capsules, the effects of K+ on [32P]Pi incorporation into PA and PI were inhibited by EGTA, but the effects of A-II on [32P]Pi incorporation were not influenced by EGTA, despite observed inhibition of steroidogenesis. Cycloheximide also inhibited steroidogenesis, but did not inhibit the effects of A-II or K+ on 32P-labeling of PA and PI. In contrast, both EGTA and cycloheximide inhibited A-II-induced increases in steroiodogenesis and PI mass. In glomerulosa cells, simple removal of Ca2+ from the medium or the addition of verapamil did not inhibit A-II effects on 32P-labeling of PA or PI; EGTA, on the other hand, inhibited the latter response. A-II and K+ provoked the breakdown of 32P-labeled PI, whereas ACTH did not. EGTA blocked the effects of A-II on PI breakdown and labeling. These inhibitory effects of EGTA in glomerulosa cells, but not in capsules, on PI hydrolysis and labeling may be due to a greater degree of Ca2+ depletion in cells, but the importance of this Ca2+ dependence is presently uncertain in view of the apparent independence of A-II effects on labeling in capsules. A23187, at lower concentrations, enhanced [32P]Pi incorporation to PA and PI mildly, but higher concentrations caused a generalized inhibition of [32P]Pi incorporation into all phospholipids. Increased labeling of PA and PI with [32P]Pi is more reflective of changes in PI hydrolysis and resynthesis (via diglyceride and PA) than the increase in de novo synthesis of PA and PI; A-II and K+ provoke PI hydrolysis and labeling by considerably different mechanisms; and the [32P]Pi-labeling effect occurs proximal to the cycloheximide-sensitive step in steroidogenesis, whereas the increase in de novo synthesis of PA and PI and polyphosphoinositides (PPI) is distal. A-II apparently provokes PI hydrolysis via receptor activation, and this, in turn, leads to Ca2+ mobilization and subsequently to increases in de novo synthesis of PA, PI, and PPI. K+ may provoke PI hydrolysis and labeling via increases in Ca2+, and the PI hyrolysis effect may further mobilize intracellular Ca2+ and consequently increase de novo synthesis of PA, PI, and PPI. ACTH, via cAMP, appears to only increase de novo synthesis of PA, PI and PPI. The de novo effect, which is common in the action of all agents, may be important for effecting increases in steroidogenesis.

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