Mechanism of angiotensin II-induced phospholipase D activation in bovine adrenal glomerulosa cells

Wendy B. Bollag, Eun Mi Jung, Roberto A. Calle

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7-16
Number of pages10
JournalMolecular and Cellular Endocrinology
Issue number1-2
StatePublished - Jun 28 2002


  • Aldosterone secretion
  • Calcium channels
  • Phosphatidic acid
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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