| Abstract: | The role of prostaglandins (PGs) in aldosterone secretion was studied in isolated rat adrenal glomerulosa cells. 14C]Arachidonic acid was metabolized to 14C]6-keto-PGF1 alpha, 14C]PGF2 alpha, 14C]PGE2, and 14C]PGD2. Pretreatment with indomethacin (5 X 10(-5) M) or U-51605 (5 micrograms/ml) inhibited the synthesis of these metabolites. Angiotensin II (AII) stimulated a concentration-related release of aldosterone and 6-keto-PGF1 alpha, but not PGE2. Significant increases in aldosterone and 6-keto-PGF1 alpha occurred at AII concentrations of 0.2 and 2 nM. The increases in 6-keto PGF1 alpha concentrations after AII treatment were small, however (278 +/- 33 pg/10(6) cells X h for control vs. 581 +/- 90 after 2 nM AII). At higher concentrations, AII further stimulated aldosterone, but 6-keto PGF1 alpha levels declined. AII stimulated the synthesis of aldosterone and 6-keto PGF1 alpha in parallel with time of incubation. Indomethacin (3 microM) decrease basal and AII-stimulated aldosterone release by 40% and 23%, respectively, and inhibited the synthesis of PGs. U-51605 (5 micrograms/ml) failed to alter aldosterone release. Arachidonic acid increased the synthesis of PGE2 and 6-keto-PGF1 alpha in a concentration-related manner without altering the synthesis of aldosterone. In contrast, PGH2 stimulated the release of PGE2, 6-keto-PGF1 alpha, and aldosterone. PGI2 and PGE2 stimulated aldosterone secretion, which was concentration related. Threshold stimulation by PGI2 and PGE2 occurred at 0.5 and 5 nM, respectively. Maximal stimulation occurred at 5 nM for PGI2 and at 5000 nM for PGE2, with PGE2 producing the greater maximal response. Treatment of the cells with trypsin eliminated the steroidogenic response to PGE2. These findings indicate that PGI2 and PGE2 are produced by the adrenal glomerulosa cells, and the synthesis of PGI2 may be stimulated by AII. However, the concentrations of PGI2 synthesized are not adequate to stimulate aldosterone secretion. Thus, PGI2 does not appear to mediate angiotensin-induced aldosterone secretion. |
