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AMP-activated protein kinase : a physiological off switch for murine gastric acid secretion

Sidani, Shafik and Kopic, Sascha and Socrates, Thenral and Kirchhoff, Philipp and Föller, Michael and Murek, Michael and Capasso, Anna and Geibel, John P.. (2009) AMP-activated protein kinase : a physiological off switch for murine gastric acid secretion. Pflügers Archiv : European journal of physiology, Vol. 459. pp. 39-46.

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Official URL: http://edoc.unibas.ch/dok/A6003465

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Abstract

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been shown to be a metabolic energy regulator in various cells. Activation is a direct result of rising AMP concentration coupled with falling adenosine triphosphate (ATP). AMPK activation during metabolic stress consequently reduces cellular ATP consumption. The gastric parietal cell has a large abundance of mitochondria per cell volume due to the numerous energy-dependent transporters and channels responsible for acid secretion. We identified AMPK in the parietal cell as a metabolic energy regulator that can switch acid secretion off as cellular ATP levels fall. AMPK presence in murine gastric glands was evaluated by immunofluorescent localization. We used a digital imaging system to monitor acid secretion as observed by proton efflux from parietal cells in hand-dissected gastric glands loaded with the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein. Individual murine gastric glands were exposed to histamine, pentagastrin, or carbachol. AMPK was pharmacologically activated with 5-aminoimidazole-4-carboxamide-1-beta-D: -riboside (AICAR) monophosphate or inhibited with 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine (compound C) or ATP. Acid secretion was evaluated under these conditions as the rate of intracellular pH recovery. In addition, whole-stomach pH measurements were performed. Immunofluorescent localization confirmed the presence of AMPK in gastric mucosa. Exposure to AICAR monophosphate significantly reduced secretagogue-induced acid secretion; addition of compound C or ATP restored acid secretion. Our results indicate that secretagogue-induced acid secretion could be significantly reduced with AMPK activation and restored with its deactivation. We therefore propose the AMPK as a cellular metabolic off switch for gastric acid secretion.
Faculties and Departments:03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe > Allgemein- und Viszeralchirurgie (Oertli)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Innere Organe > Allgemein- und Viszeralchirurgie (Oertli)
UniBasel Contributors:Kirchhoff, Philipp
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Springer
ISSN:0031-6768
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:01 Mar 2013 11:14
Deposited On:01 Mar 2013 11:11

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