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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/E423    most recent 00128.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Gambaryan, S. Articles by Walter, U. Search for Related Content PubMed PubMed Citation Articles by Gambaryan, S. Articles by Walter, U.

Regulation of aldosterone production from zona glomerulosa cells by ANG II and cAMP: evidence for PKA-independent activation of CaMK by cAMP

¹Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg; ²Department of Anesthesiology; ³Endocrinology and Diabetes Unit, Medical University Clinic Würzburg, Wurzburg; and ⁴Institute of Biochemistry II Medical University Clinic Frankfurt, Frankfurt, Germany

Submitted 21 March 2005 ; accepted in final form 6 October 2005

Aldosterone production in zona glomerulosa (ZG) cells of adrenal glands is regulated by various extracellular stimuli (K⁺, ANG II, ACTH) that all converge on two major intracellular signaling pathways: an increase in cAMP production and calcium (Ca²⁺) mobilization. However, molecular events downstream of the increase in intracellular cAMP and Ca²⁺ content are controversial and far from being completely resolved. Here, we found that Ca²⁺/calmodulin-dependent protein kinases (CaMKs) play a predominant role in the regulation of aldosterone production stimulated by ANG II, ACTH, and cAMP. The specific CaMK inhibitor KN93 strongly reduced ANG II-, ACTH-, and cAMP-stimulated aldosterone production. In in vitro kinase assays and intact cells, we could show that cAMP-induced activation of CaMK, using the adenylate cyclase activator forskolin or the cAMP-analog Sp-5,6-DCI-cBIMPS (cBIMPS), was not mediated by PKA. Activation of the recently identified cAMP target protein Epac (exchange protein directly activated by cAMP) by 8-pCPT-2'-O-Me-cAMP had no effect on CaMK activity and aldosterone production. Furthermore, we provide evidence that cAMP effects in ZG cells do not involve Ca²⁺ or MAPK signaling. Our results suggest that ZG cells, in addition to PKA and Epac/Rap proteins, contain other as yet unidentified cAMP mediator(s) involved in regulating CaMK activity and aldosterone secretion.

angiotension II; adenosine 3',5'-cyclic monophosphate; adenosine 3',5'-cyclic monophosphate-dependent protein kinase; Ca²⁺/calmodulin-dependent kinase

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