Aspects of angiotensin action in the adrenal. Key roles for calcium and phosphatidyl inositol.
The steps between exposure of bovine adrenal glomerulosa cells to angiotensin and the stimulated increase in aldosterone production were studied in two ways. Binding of angiotensin to receptors, and hormone effects on phosphatidyl inositol turnover, 45Ca2+ fluxes, and aldosterone production were measured directly. Other potential intermediate steps were investigated indirectly by use of inhibitors. Angiotensin slowed calcium influx and accelerated phosphatidyl inositol turnover in proportion to hormone dose. The effects correlated with receptor binding and aldosterone production. None of the inhibitors tested, except saralasin, inhibited angiotensin's effect on phosphatidyl inositol turnover. Altered calcium flux and stimulated aldosterone production were affected by the calmodulin inhibitor trifluoperazine and the intracellular calcium antagonist 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8). Several reagents did not affect angiotensin binding, its effect on phosphatidyl inositol, or 45Ca2+ flux, but severely inhibited steroidogenesis. These included the phospholipase A2 inhibitor mepacrine, the protein synthesis inhibitor cycloheximide, and the Na+/k+-ATPase inhibitor ouabain. Colchicine had very little effect on the processes we measured, suggesting that microtubules play no role in angiotensin action in the adrenal. Based o these observations, we propose that angiotensin II affects the adrenal glomerulosa cell by first interacting with receptors, then increasing phosphatidyl inositol turnover, then altering cellular calcium distribution. Step distal to altered calcium distribution that contribute to increased steroid output include altered phospholipid metabolism, protein synthesis, and Na/k metabolism.
D000302:Adrenal Cortex / Q000187:drug effects* / Q000502:physiology; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000096:biosynthesis; D002417:Cattle; D007473:Ion Channels / Q000502:physiology; D010716:Phosphatidylinositols / Q000502:physiology*; D010741:Phospholipases A / Q000502:physiology; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D014176:Protein Biosynthesis; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology
D002147:Calmodulin; D007473:Ion Channels; D010716:Phosphatidylinositols; D010743:Phospholipids; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000450:Aldosterone; D010741:Phospholipases A; D054467:Phospholipases A2; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium