TY - JOUR
T1 - Mechanism of angiotensin II-induced phospholipase D activation in bovine adrenal glomerulosa cells
AU - Bollag, Wendy B.
AU - Jung, Eun Mi
AU - Calle, Roberto A.
N1 - Funding Information:
We thank the Shapiro Meat Packing Company and William Brown for providing adrenal glands and Natalia Foley, Stephanie White, Mariya Malinova, Patricia Kent and Peter Parker for their expert technical assistance. This work was supported by an American Heart Association/Southeast affiliate Grant-in-Aid (to W.B. Bollag) and a Veteran's Administration Merit Review Award and American Heart Association/Southeast affiliate Grant-in-Aid (to R.A. Calle). This work has been presented in part at the 79th Annual Meeting of the Endocrine Society, June 1997 in Minneapolis, MN, and the 82nd Annual Meeting of the Endocrine Society, June 2000 in Toronto, Canada.
PY - 2002/6/28
Y1 - 2002/6/28
N2 - Based on previous data demonstrating activation of phospholipase D (PLD) in response to angiotensin II (AngII), we have hypothesized a role for PLD in mediating aldosterone secretion from bovine adrenal glomerulosa cells. In this study we demonstrate that a PLD-generated signal(s) is required for the AngII-elicited secretory response, since interfering with lipid second messenger formation using a primary alcohol inhibited AngII-induced aldosterone secretion, but not that elicited by incubation with a hydrophilic cholesterol analog, 22(R)-hydroxycholesterol, which bypasses signaling pathways. Three mechanisms for hormonal activation of PLD have been described in other systems: direct receptor coupling, activation through protein kinase C (PKC) and a combination of these two mechanisms. Our results indicate that the PKC activator, phorbol 12-myristic 13-acetate (PMA), is able to activate PLD, and that receptor engagement is apparently not necessary for PLD activation in response to this agent. Maximal doses of AngII and PMA produced no additive effect on PLD activation, suggesting that these two agents function through a common PKC pathway. This interpretation was confirmed by the ability of a PKC inhibitor, Gö 6976, to inhibit partially AngII-induced PLD activation. Finally, treatment with the calcium ionophores A23187 or ionomycin or the calcium channel agonist BAY K8644 had no effect on PLD activity. Likewise, inhibiting calcium influx with high-dose nitrendipine affected neither basal PLD activity nor that stimulated by AngII. Thus, our results suggest a role for PKC, independent of calcium influx, in mediating AngII-induced PLD activation in glomerulosa cells.
AB - Based on previous data demonstrating activation of phospholipase D (PLD) in response to angiotensin II (AngII), we have hypothesized a role for PLD in mediating aldosterone secretion from bovine adrenal glomerulosa cells. In this study we demonstrate that a PLD-generated signal(s) is required for the AngII-elicited secretory response, since interfering with lipid second messenger formation using a primary alcohol inhibited AngII-induced aldosterone secretion, but not that elicited by incubation with a hydrophilic cholesterol analog, 22(R)-hydroxycholesterol, which bypasses signaling pathways. Three mechanisms for hormonal activation of PLD have been described in other systems: direct receptor coupling, activation through protein kinase C (PKC) and a combination of these two mechanisms. Our results indicate that the PKC activator, phorbol 12-myristic 13-acetate (PMA), is able to activate PLD, and that receptor engagement is apparently not necessary for PLD activation in response to this agent. Maximal doses of AngII and PMA produced no additive effect on PLD activation, suggesting that these two agents function through a common PKC pathway. This interpretation was confirmed by the ability of a PKC inhibitor, Gö 6976, to inhibit partially AngII-induced PLD activation. Finally, treatment with the calcium ionophores A23187 or ionomycin or the calcium channel agonist BAY K8644 had no effect on PLD activity. Likewise, inhibiting calcium influx with high-dose nitrendipine affected neither basal PLD activity nor that stimulated by AngII. Thus, our results suggest a role for PKC, independent of calcium influx, in mediating AngII-induced PLD activation in glomerulosa cells.
KW - Aldosterone secretion
KW - Calcium channels
KW - Phosphatidic acid
KW - Protein kinase C
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U2 - 10.1016/S0303-7207(02)00134-X
DO - 10.1016/S0303-7207(02)00134-X
M3 - Article
C2 - 12088862
AN - SCOPUS:0037188810
SN - 0303-7207
VL - 192
SP - 7
EP - 16
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -