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

• Published in: Pflügers Archiv Vol. 466; no. 10; pp. 2009 - 2018
• Main Authors: Schramm, Andrea, Schinner, Elisabeth, Huettner, Johannes P., Kees, Frieder, Tauber, Philipp, Hofmann, Franz, Schlossmann, Jens
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2014; Springer Nature B.V
• Subjects: Animals; Aquaporin 2 - genetics; Aquaporin 2 - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Membrane - metabolism; Cyclic GMP-Dependent Protein Kinase Type II - genetics; Cyclic GMP-Dependent Protein Kinase Type II - metabolism; Diuresis; Glucose - pharmacology; Human Physiology; Kidney - drug effects; Kidney - metabolism; Kidney - physiology; Mice; Molecular Medicine; Neurosciences; Phosphorylation; Protein Transport; Receptors; Renal Elimination; Signaling and Cell Physiology; Sodium - metabolism; Diuresis; cGMP; cGKII; AQP2; Kidney
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-014-1445-y

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.