Role of the serum and glucocorticoid inducible kinase SGK1 in glucocorticoid stimulation of gastric acid secretion
| Autor: | Florian Lang, Lothar Just, Thomas Skutella, Diana Sandulache, Björn Friedrich, Peer Wulff, Anand Rotte, Andreas F. Mack, Ferruh Artunc, Krishna M. Boini, Teut Risler, Ciprian D. Sandu, Dietmar Kuhl, Marco Metzger, Rexhep Rexhepaj, Florian Grahammer |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Carbachol Physiology Clinical Biochemistry Stimulation Biology Protein Serine-Threonine Kinases Dexamethasone Immediate-Early Proteins Gastric Acid chemistry.chemical_compound Mice Parietal Cells Gastric Physiology (medical) Internal medicine Gastric glands medicine Animals Secretion Forskolin urogenital system Colforsin Hydrogen-Ion Concentration Endocrinology medicine.anatomical_structure chemistry KCNQ1 Potassium Channel SGK1 Gastric acid Corticosterone Glucocorticoid medicine.drug |
| Zdroj: | Pflugers Archiv : European journal of physiology. 455(3) |
| ISSN: | 0031-6768 |
| Popis: | Glucocorticoids stimulate gastric acid secretion, an effect favoring the development of peptic ulcers. Putative mechanisms involved include the serum- and glucocorticoid-inducible kinase (SGK1), which stimulates a variety of epithelial channels and transporters. The present study explored the contribution of SGK1 to effects of glucocorticoids on gastric acid secretion. In isolated gastric glands from gene-targeted mice lacking functional SGK1 (sgk1 (-/-)) and their wild-type littermates (sgk1 (+/+)), H(+)-secretion (DeltapH/min) was determined utilizing 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-fluorescence, SGK1 transcript levels by in situ hybdridization, and expression of KCNQ1 channels by immunohistochemistry and real-time polymerase chain reaction. SGK1 transcript levels were enhanced by a 4-day treatment with 10 mug/g body weight (BW)/day dexamethasone (DEX). Before treatment, DeltapH/min was similar in sgk1 (-/-) and sgk1 (+/+)mice. DEX increased DeltapH/min approximately fourfold in sgk1 (+/+)mice and approximately twofold in sgk1 (-/-)mice, effects abolished in the presence of K(+)/H(+)ATPase-inhibitor omeprazole (50 microM). Increase in local K(+) concentrations to 35 mM (replacing Na(+)) enhanced DeltapH/min, which could not be further stimulated by DEX and was not significantly different between sgk1 (-/-) and sgk1 (+/+)mice. Carbachol (100 microM) and forskolin (5 microM) stimulated gastric acid secretion to a similar extent in sgk1 (-/-) and sgk1 (+/+)mice. In conclusion, SGK1 is not required for basal and cyclic AMP-stimulated gastric H(+) secretion but participates in the stimulation of gastric H(+) secretion by glucocorticoids. The effects of glucocorticoids and SGK1 are not additive to an increase in extracellular K(+) concentration and may thus involve stimulation of K(+) channels. |
| Databáze: | OpenAIRE |
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