Functional role of extracellular signal-regulated protein kinases in gastric acid secretion

The American Journal of Physiology
Y TakeuchiA Todisco

Abstract

Epidermal growth factor (EGF) has acute inhibitory and chronic stimulatory effects on gastric acid secretion. Because a cascade of intracellular events culminating in the activation of a family of serine-threonine protein kinases called extracellular signal-regulated protein kinases (ERKs) is known to mediate the actions of EGF, we undertook studies to explore the functional role of the ERKs in gastric acid secretion. ERK2 was immunoprecipitated from cell lysates of highly purified (> 95%) gastric canine parietal cells, and its activity was quantified using in-gel kinase assays. Of the primary gastric secretagogues, carbachol was the most potent inducer of ERK2 activity. Gastrin and EGF had weaker stimulatory effects, whereas no induction was noted in response to histamine. The effect of carbachol appeared to be independent of Ca2+ signaling. PD-98059, a selective inhibitor of the upstream ERK activator mitogen-activated protein kinase/ERK kinase, dose-dependently inhibited both carbachol- and EGF-stimulated ERK2 activity, with a maximal effect observed between 50 and 100 microM. ERKs activation is required for induction of the early gene c-fos via phosphorylation of the transcription factor Elk-1 which binds to the c-fos serum...Continue Reading

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Citations

Jan 25, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·N PausawasdiA Todisco
Feb 22, 2001·Annual Review of Physiology·G J DockrayT Wang
Jun 22, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·M GöõzA J Smolka
May 9, 2002·American Journal of Physiology. Renal Physiology·Amy E FrankI David Weiner
Jan 11, 2013·Physiological Reviews·Sascha Kopic, John P Geibel
Apr 7, 2007·Experimental Physiology·Rod Dimaline, Andrea Varro
Jun 24, 2008·Experimental Physiology·Adelina PaglioccaGraham J Dockray
Dec 26, 2002·Annual Review of Physiology·Xuebiao Yao, John G Forte
Oct 21, 2003·Journal of Cellular Physiology·Keiichiro TashiroTetsuro Urushidani
May 23, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Nonthalee PausawasdiAndrea Todisco
Nov 6, 2009·American Journal of Physiology. Cell Physiology·Sascha KopicJohn P Geibel

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