Stimulation of phosphatidylinositol turnover by acetylcholine, angiotensin II and ACTH in bovine adrenal fasciculata cells

Abstract

The effect of acetylcholine, angiotensin II and adrenocorticotropin (ACTH) on phosphatidylinositol (PI) metabolism was examined using bovine adrenocortical fasciculata cell suspensions. The three agents, which acutely stimulate glucocorticoid production by these cells, were all able to increase [ 32P]P i incorporation into cellular PI. However, whereas the relative steroidogenic potency (at maximally active concentrations) was ACTH ⩾ angiotensin II > acetylcholine, the effect on PI labeling was in the order angiotensin II > acetylcholine > ACTH. The dose-response curves for steroidogenesis and that for PI labeling were superimposable in the case of angiotensin II (ED 50=1·10 −8 M) and of acetylcholine (ED 50=5·10 −7 M), while the two responses were dissociated under graded ACTH challenge. Both steroidogenic response and increased PI labeling elicited by angiotensin II and acetylcholine were respectively inhibited by (Sar 1-Ala 8)-angiotensin II and muscarinic antagonists. Time-course study showed that in the case of angiotensin II and acetylcholine, the sequence of events was: increased phosphatidic acid labeling, increased PI labeling, activated steroidogenesis. By sharp contrast, under ACTH stimulation, increased steroidogenesis was detected well before activation of PI metabolism. These data suggest that in bovine adrenocortical fasciculata cell, steroidogenesis may be activated by two different pathways. The first one would act mainly through cyclic AMP-dependent intracellular events and is usually accepted in the mechanism of action of ACTH. The other, cyclic AMP-independent pathway, as in the case of angiotensin II and acetylcholine actions, may involve phospholipid-mediated intracellular processes.