TY - JOUR
T1 - Angiotensin II-stimulated phosphatidylinositol turnover in rat adrenal glomerulosa cells has a complex dependence on calcium
AU - Woodcock, Elizabeth A.
AU - Smith, A. Ian
AU - Schmauk White, L. Barbara
PY - 1988/3/1
Y1 - 1988/3/1
N2 - 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-(l,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.
AB - 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-(l,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.
UR - http://www.scopus.com/inward/record.url?scp=0023902354&partnerID=8YFLogxK
U2 - 10.1210/endo-122-3-1053
DO - 10.1210/endo-122-3-1053
M3 - Article
C2 - 2830094
AN - SCOPUS:0023902354
SN - 0013-7227
VL - 122
SP - 1053
EP - 1059
JO - Endocrinology
JF - Endocrinology
IS - 3
ER -