Schramm, Andrea and Schinner, Elisabeth and Huettner, Johannes P. and Kees, Frieder and Tauber, Philipp and Hofmann, Franz and Schlossmann, Jens (2014) Function of cGMP-dependent protein kinase II in volume load-induced diuresis. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 466 (10). pp. 2009-2018. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MEDULLARY COLLECTING DUCT; RENAL EPITHELIAL-CELLS; NATRIURETIC-PEPTIDE; NITRIC-OXIDE; RAT-KIDNEY; MEMBRANE INSERTION; SODIUM RETENTION; WATER CHANNELS; MICE LACKING; EXPRESSION; cGMP; cGKII; Kidney; Diuresis; AQP2 |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 615 Pharmacy |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Aug 2019 11:20 |
| Last Modified: | 13 Aug 2019 11:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9512 |
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