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Regulation of gastric acid secretion by the serum and glucocorticoid inducible kinase isoform SGK3

  • Original Article—Alimentary Tract
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Abstract

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 (100 μM) and SCH28080 (500 nM). Increase of extracellular K+ concentrations to 35 mM (replacing Na+/NMDG) or treatment with 5 μM 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 (150 nM) 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.

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Abbreviations

BCECF:

2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester

DMSO:

Dimethylsulfoxide

NMDG:

N-methyl d-glucamine

HEPES:

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

FSK:

Forskolin

omp:

Omeprazole

SGK:

Serum and glucocorticoid inducible kinase

PDK:

Phosphoinositide-dependent kinase

PI3K:

Phosphoinositol 3 kinase

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Acknowledgments

The authors gratefully acknowledge the meticulous preparation of the manuscript by Tanja Loch. This work was supported by grants from the DFG (SFB 773). All authors of this manuscript have no conflicts of interests.

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Authors and Affiliations

  1. Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Venkanna Pasham, Anand Rotte, Madhuri Bhandaru, Melanie Eichenmüller, Henning Fröhlich, Diwakar Bobbala, Wenting Yang & Florian Lang

  2. Department of Anatomy, University of Tübingen, Tübingen, Germany

    Andreas F. Mack

  3. Department of Medicine (Nephrology), University of California, San Francisco, CA, 94122, USA

    David Pearce

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  1. Venkanna Pasham
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  2. Anand Rotte
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Correspondence to Florian Lang.

Additional information

V. Pasham and A. Rotte contributed equally and thus share first authorship.

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Pasham, V., Rotte, A., Bhandaru, M. et al. Regulation of gastric acid secretion by the serum and glucocorticoid inducible kinase isoform SGK3. J Gastroenterol 46, 305–317 (2011). https://doi.org/10.1007/s00535-010-0348-8

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  • DOI: https://doi.org/10.1007/s00535-010-0348-8

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