caa a22 4500 445888458 CHVBK 20180317145607.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00535-010-0348-8 doi (NATIONALLICENCE)springer-10.1007/s00535-010-0348-8 Regulation of gastric acid secretion by the serum and glucocorticoid inducible kinase isoform SGK3 [Elektronische Daten] [Venkanna Pasham, Anand Rotte, Madhuri Bhandaru, Melanie Eichenmüller, Henning Fröhlich, Andreas Mack, Diwakar Bobbala, Wenting Yang, David Pearce, Florian Lang] Background: The serum and glucocorticoid inducible kinase isoform SGK3 is ubiquitously expressed and has been shown to participate in the regulation of cell survival and transport. Similar to SGK1 and protein kinase B (PKB/Akt) isoforms, SGK3 may phosphorylate glycogen synthase kinase (GSK) 3α,β, which has recently been shown to participate in the regulation of basal gastric acid secretion. The present study thus explored the role of SGK3 in the regulation of gastric acid secretion. Methods: Experiments were performed in isolated glands from gene-targeted mice lacking functional SGK3 (sgk3 −/−) or from their wild-type littermates (sgk3 +/+). Utilizing 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester (BCECF) fluorescence, gastric acid secretion was determined from Na+-independent pH recovery (∆pH/min) following an ammonium pulse, which reflects H+/K+ adenosine triphosphatase (ATP) ase activity. Results: Cytosolic pH in isolated gastric glands was similar in sgk3 −/− and sgk3 +/+ mice. ∆pH/min was, however, significantly larger in sgk3 −/− than in sgk3 +/+ mice. In both genotypes, ∆pH/min was virtually abolished in the presence of the H+/K+ ATPase inhibitor omeprazole (100μM) and SCH28080 (500nM). Increase of extracellular K+ concentrations to 35mM (replacing Na+/NMDG) or treatment with 5μM forskolin increased ∆pH/min in sgk3 +/+ mice to a larger extent than in sgk3 −/− mice and abrogated the differences between genotypes. The protein kinase A inhibitor H89 (150nM) decreased ∆pH/min to similarly low values in both genotypes. Conclusions: SGK3 suppresses gastric acid secretion, an effect presumably mediated by the stimulation of protein kinase A with the subsequent activation of K+ channels. Springer, 2010 PI3 kinase nationallicence SGK3 nationallicence Stomach nationallicence H+/K+ ATPase nationallicence K+ recycling nationallicence H+ secretion nationallicence BCECF : 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester nationallicence DMSO : Dimethylsulfoxide nationallicence NMDG : N-methyl d-glucamine nationallicence HEPES : 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid nationallicence FSK : Forskolin nationallicence omp : Omeprazole nationallicence SGK : Serum and glucocorticoid inducible kinase nationallicence PDK : Phosphoinositide-dependent kinase nationallicence PI3K : Phosphoinositol 3 kinase nationallicence Pasham Venkanna Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut Rotte Anand Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut Bhandaru Madhuri Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut Eichenmüller Melanie Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut Fröhlich Henning Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut Mack Andreas Department of Anatomy, University of Tübingen, Tübingen, Germany aut Bobbala Diwakar Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut Yang Wenting Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut Pearce David Department of Medicine (Nephrology), University of California, 94122, San Francisco, CA, USA aut Lang Florian Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut Journal of Gastroenterology Springer Japan 46/3(2011-03-01), 305-317 0944-1174 46:3<305 2011 46 535 https://doi.org/10.1007/s00535-010-0348-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-010-0348-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pasham Venkanna Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Rotte Anand Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Bhandaru Madhuri Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Eichenmüller Melanie Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Fröhlich Henning Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Mack Andreas Department of Anatomy, University of Tübingen, Tübingen, Germany aut NATIONALLICENCE 700 1- Bobbala Diwakar Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Yang Wenting Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 700 1- Pearce David Department of Medicine (Nephrology), University of California, 94122, San Francisco, CA, USA aut NATIONALLICENCE 700 1- Lang Florian Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/3(2011-03-01), 305-317 0944-1174 46:3<305 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer