title: Role of the serum and glucocorticoid inducible kinase SGK1 in glucocorticoid stimulation of gastric acid secretion.
abstract: 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.
authors.affiliation: Department of Physiology, University of Tuebingen, Tübingen, Germany.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Sandu
authors.forename: Ferruh
authors.initials: F
authors.lastname: Artunc
authors.forename: Florian
authors.initials: F
authors.lastname: Grahammer
authors.forename: Anand
authors.initials: A
authors.lastname: Rotte
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Boini
authors.forename: Björn
authors.initials: B
authors.lastname: Friedrich
authors.forename: Diana
authors.initials: D
authors.lastname: Sandulache
authors.forename: Marco
authors.initials: M
authors.lastname: Metzger
authors.forename: Lothar
authors.initials: L
authors.lastname: Just
authors.forename: Andreas
authors.initials: A
authors.lastname: Mack
authors.forename: Thomas
authors.initials: T
authors.lastname: Skutella
authors.forename: Rexhep
authors.initials: R
authors.lastname: Rexhepaj
authors.forename: Teut
authors.initials: T
authors.lastname: Risler
authors.forename: Peer
authors.initials: P
authors.lastname: Wulff
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D017874:Immediate-Early Proteins / Q000502:physiology*; D051657:KCNQ1 Potassium Channel / Q000096:biosynthesis; D051379:Mice; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D002217:Carbachol; D005576:Colforsin; D003345:Corticosterone; D003907:Dexamethasone; D017874:Immediate-Early Proteins; D051657:KCNQ1 Potassium Channel; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C496910:Kcnq1 protein, mouse