Molecular mechanisms of ANP/cGMP-dependent inhibition of aldosterone production in adrenal gland
Final Report Abstract
A major goal of this DFG funded grant (discovery and functional characterization of a novel cGMP effector system in aldosterone producing zona glomerulosa cells) was, despite major efforts, unfortunately not achieved. However, a broad spectrum of data were obtained and published (see this report and its publication list). These included the characterization of adrenal zona glomerulosa cells from GC-A knock-out mice and the use of novel FRET based fluorescent sensors for monitoring intracellular cGMP. Also, additional evidence for protein kinase A (PKA)/protein kinase G (PKG) –independent effector systems for both cAMP and cGMP was obtained. However, a novel cGMP target could not be detected and characterized despite major efforts. Unless new results and/or developments in this field will provide new insights we do not plan to continue this line of research at present. However, we recently discovered a new mechanism of cGMP regulation including the PKG / VASP system which is the NOS-independent activation of the soluble guanylyl cyclase by von Willebrand factor (vWF) in murine and human platelets. We plan to develop this line of research further, which could be of broad interest and significance. Here, we thank the DFG for the generous support of this project which will be clearly continued.
Publications
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Inhibition of agonist-stimulated aldosterone production from adrenal zona glomerulosa cells by ANP is mediated by GC-A. 2nd International Conference on cGMP, Potsdam, 2005.
Gambaryan S, Kuhn M, Walter U.
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(2006). Fluorescent sensors for rapid monitoring of intracellular cGMP. Nat Methods. 3(1):23-25.
Nikolaev VO, Gambaryan S, Lohse MJ.
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(2006). Regulation of aldosterone production from zona glomerulosa cells by Ang II and cAMP: Evidence for PKA independent activation of CaMK by cAMP. Amer. J. Physiol., 290: E423-433.
Gambaryan S, Butt E, Tas P, Smolenski A, Allolio B, Walter U
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(2007) Thrombin stimulation of p38 MAP kinase in human platelets is mediated by ADP and thromboxane A2 and inhibited by cGMP/cGMP-dependent protein kinase. Blood, 109, 616-618
Begonja AJ, Geiger J, Rukoyatkina N, Rauchfuss S, Gambaryan S, Walter, U
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(2007). Phosphodiesterase 2A forms a complex with the Co-chaperone XAP2 & regulates nuclear translocation of the aryl hydrocarbon receptor. J. Biol. Chem. 282: 13656-13663.
Oliveira KS, Hoffmeister M, Gambaryan S, Mueller-Esterl W, Guimaraes JA, Smolenski AP
