TY - JOUR
T1 - The role of calcium influx pathways in phospholipase D activation in bovine adrenal glomerulosa cells
AU - Qin, Haixia
AU - Kent, Patricia
AU - Isales, Carlos M.
AU - Parker, Peter M.
AU - Wilson, Mariya V.
AU - Bollag, Wendy B.
PY - 2009
Y1 - 2009
N2 - The steroid hormone aldosterone maintains sodium homeostasis and is therefore important in the control of blood volume and pressure. Angiotensin II (AngII) and elevated extracellular potassium concentrations ([K+]e), the prime physiologic regulators of aldosterone secretion from adrenal glomerulosa cells, activate phospholipase D (PLD) in these cells. The role of Ca2+ in the activation by these agents is unknown, although nitrendipine, a voltage-dependent Ca2C channel antagonist, does not inhibit AngII-elicited PLD activation, despite the fact that this compound blocked elevated [K+]e-stimulated PLD activity. PLD activation triggered by AngII was also unaffected by the T-type calcium channel inhibitor nickel. Nevertheless, Ca2+ influx was required for AngII-induced PLD activation in both primary cultures of bovine adrenal glomerulosa cells and a glomerulosa cell model, the NCI H295R adrenocortical carcinoma cell line. The involvement of store-operated Ca2+ (SOC) influx and Ca2+ release-activated Ca2+ (CRAC) influx pathways in PLD activation was investigated using thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor that empties the store to induce SOC influx, and the SOC inhibitor YM-58483 (BTP2), as well as a CRAC inhibitor, tyrphostin A9. In bovine glomerulosa cells, tyrphostin A9 inhibited AngII-induced PLD activation without affecting elevated [K+]e-stimulated enzyme activity. On the other hand, differences were observed between the bovine adrenal glomerulosa and H295R cells in the involvement of Ca2+ influx pathways in PLD activation, with the involvement of the SOC pathway suggested in the H295R cells. In summary, our results indicate that Ca2+ entry only through certain Ca2+ influx pathways is linked to PLD activation.
AB - The steroid hormone aldosterone maintains sodium homeostasis and is therefore important in the control of blood volume and pressure. Angiotensin II (AngII) and elevated extracellular potassium concentrations ([K+]e), the prime physiologic regulators of aldosterone secretion from adrenal glomerulosa cells, activate phospholipase D (PLD) in these cells. The role of Ca2+ in the activation by these agents is unknown, although nitrendipine, a voltage-dependent Ca2C channel antagonist, does not inhibit AngII-elicited PLD activation, despite the fact that this compound blocked elevated [K+]e-stimulated PLD activity. PLD activation triggered by AngII was also unaffected by the T-type calcium channel inhibitor nickel. Nevertheless, Ca2+ influx was required for AngII-induced PLD activation in both primary cultures of bovine adrenal glomerulosa cells and a glomerulosa cell model, the NCI H295R adrenocortical carcinoma cell line. The involvement of store-operated Ca2+ (SOC) influx and Ca2+ release-activated Ca2+ (CRAC) influx pathways in PLD activation was investigated using thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor that empties the store to induce SOC influx, and the SOC inhibitor YM-58483 (BTP2), as well as a CRAC inhibitor, tyrphostin A9. In bovine glomerulosa cells, tyrphostin A9 inhibited AngII-induced PLD activation without affecting elevated [K+]e-stimulated enzyme activity. On the other hand, differences were observed between the bovine adrenal glomerulosa and H295R cells in the involvement of Ca2+ influx pathways in PLD activation, with the involvement of the SOC pathway suggested in the H295R cells. In summary, our results indicate that Ca2+ entry only through certain Ca2+ influx pathways is linked to PLD activation.
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U2 - 10.1677/JOE-09-0119
DO - 10.1677/JOE-09-0119
M3 - Article
C2 - 19372190
AN - SCOPUS:67650710978
SN - 0022-0795
VL - 202
SP - 77
EP - 86
JO - Journal of Endocrinology
JF - Journal of Endocrinology
IS - 1
ER -