Angiotensin II-activated protein kinase D mediates acute aldosterone secretion

Brian A. Shapiro, Lawrence Olala, Senthil Nathan Arun, Peter M. Parker, Mariya V. George, Wendy B. Bollag

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Dysregulation of the renin-angiotensin II (AngII)-aldosterone system can contribute to cardiovascular disease, such that an understanding of this system is critical. Diacylglycerol-sensitive serine/threonine protein kinase D (PKD) is activated by AngII in several systems, including the human adrenocortical carcinoma cell line NCI H295R, where this enzyme enhances chronic (24 h) AngII-evoked aldosterone secretion. However, the role of PKD in acute AngII-elicited aldosterone secretion has not been previously examined. In primary cultures of bovine adrenal glomerulosa cells, which secrete detectable quantities of aldosterone in response to secretagogues within minutes, PKD was activated in response to AngII, but not an elevated potassium concentration or adrenocorticotrophic hormone. This activation was time- and dose-dependent and occurred through the AT1, but not the AT2, receptor. Adenovirus-mediated overexpression of constitutively active PKD resulted in enhanced AngII-induced aldosterone secretion; whereas overexpression of a dominant-negative PKD construct decreased AngII-stimulated aldosterone secretion. Thus, we demonstrate for the first time that PKD mediates acute AngII-induced aldosterone secretion.

Original languageEnglish (US)
Pages (from-to)99-105
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume317
Issue number1-2
DOIs
StatePublished - Apr 12 2010

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Keywords

  • Adrenal cortex
  • Bovine adrenal gland
  • Glomerulosa cell
  • Hypertension
  • Protein kinase C (PKC)
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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