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- Title
Function of cGMP-dependent protein kinase II in volume load-induced diuresis.
- Authors
Schramm, Andrea; Schinner, Elisabeth; Huettner, Johannes; Kees, Frieder; Tauber, Philipp; Hofmann, Franz; Schlossmann, Jens
- 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.
- Subjects
CYCLIC guanylic acid; PROTEIN kinases; DIURESIS; ATRIAL natriuretic peptides; NATRIURESIS; ETIOLOGY of diseases
- Publication
Pflügers Archiv: European Journal of Physiology, 2014, Vol 466, Issue 10, p2009
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-014-1445-y