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Function of cGMP-dependent protein kinase II in volume load-induced diuresis

  • Signaling and cell physiology
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Abstract

Atrial natriuretic peptide (ANP)/cGMPs cause diuresis and natriuresis. Their downstream effectors beyond cGMP remain unclear. To elucidate a probable function of cGMP-dependent protein kinase II (cGKII), we investigated renal parameters in different conditions (basal, salt diets, starving, water load) using a genetically modified mouse model (cGKII-KO), but did not detect any striking differences between WT and cGKII-KO. Thus, cGKII is proposed to play only a marginal role in the adjustment of renal concentration ability to varying salt loads without water restriction or starving conditions. When WT mice were subjected to a volume load (performed by application of a 10-mM glucose solution (3 % of BW) via feeding needle), they exhibited a potent diuresis. In contrast, urine volume was decreased significantly in cGKII-KO. We showed that AQP2 plasma membrane (PM) abundance was reduced for about 50 % in WT upon volume load, therefore, this might be a main cause for the enhanced diuresis. In contrast, cGKII-KO mice almost completely failed to decrease AQP2-PM distribution. This significant difference between both genotypes is not induced by an altered p-Ser256-AQP2 phosphorylation, as phosphorylation at this site decreases similarly in WT and KO. Furthermore, sodium excretion was lowered in cGKII-KO mice during volume load. In summary, cGKII is only involved to a minor extent in the regulation of basal renal concentration ability. By contrast, cGKII-KO mice are not able to handle an acute volume load. Our results suggest that membrane insertion of AQP2 is inhibited by cGMP/cGKII.

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Acknowledgements

We thank Astrid Seefeld and Gertraud Wilberg for their excellent technical assistance. The work was supported by the Bavarian state, Sonderforschungsbereich SFB699, and Deutsche Forschungsgemeinschaft DFG.

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Authors and Affiliations

  1. Pharmacology and Toxicology, Institute of Pharmacy, University of Regensburg, Universitätsstr 31, 93053, Regensburg, Germany

    Andrea Schramm, Elisabeth Schinner, Johannes P. Huettner, Frieder Kees & Jens Schlossmann

  2. Medical Cell biology, Institute of Physiology, University of Regensburg, Regensburg, Germany

    Philipp Tauber

  3. Carvas, Technical University Munich, Munich, Germany

    Franz Hofmann

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  1. Andrea Schramm
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Schramm, A., Schinner, E., Huettner, J.P. et al. Function of cGMP-dependent protein kinase II in volume load-induced diuresis. Pflugers Arch - Eur J Physiol 466, 2009–2018 (2014). https://doi.org/10.1007/s00424-014-1445-y

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