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Angiotensin II-stimulated phosphatidylinositol turnover in rat adrenal glomerulosa cells has a complex dependence on
E A Woodcock1, A I Smith, L B White
1Department of Medicine, Monash University, Melbourne, Australia.
Abstract:
The stimulation of phosphatidylinositol (PI) turnover by angiotensin II in rat adrenal glomerulosa cells has been studied in detail and shown to have a complex dependence on Ca2+. After the addition of angiotensin II, inositol monophosphate, inositol bisphosphate, and inositol trisphosphate increased rapidly and transiently. The transient increase was followed by a slower sustained rise, which continued for up to 30 min. Inositol phosphate accumulation during the sustained phase was decreased when experiments were performed in Ca2+-free medium. The initial transient response was not altered. Addition of the Ca2+ ionophore A23187 enhanced the angiotensin II response at 20 min, but not the 15 sec response. The sustained response, but not the transient response, was attenuated by the Ca2+ channel blocker nifedipine, indicating that the effect of Ca2+ required uptake through voltage-dependent Ca2+ channels. Subsequent studies showed that cAMP decreased inositol phosphate accumulation at 20 min while having no effect at 15 sec. Also, incubation with phorbol 12-myristate 13-acetate produced a more effective inhibition of the sustained response than of the initial transient response. However, while the transient and sustained phases of PI turnover were differently affected by Ca2+ and inhibitory compounds, the profiles of inositol phosphates generated were similar. At both 15 sec and 20 min inositol-(1,4,5) trisphosphate was detected, indicating sustained cleavage of PI-(4,5) bisphosphate. Taken together, the results suggest that while the initial PI turnover response is independent of Ca2+ and presumably initiates the rise in cytosolic Ca2+, sustained response requires entry of Ca2+ to maintain elevated cytosolic Ca2+ concentrations. Thus, while the increase in cytosolic Ca2+ may have a direct role in the stimulation of aldosterone synthesis, it is also required to sustain the PI turnover response to angiotensin II.