Document Detail

AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion.
MedLine Citation:
PMID:  19621238     Owner:  NLM     Status:  MEDLINE    
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.
Shafik Sidani; Sascha Kopic; Thenral Socrates; Philipp Kirchhoff; Michael F??ller; Michael Murek; Anna Capasso; John P Geibel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-07-21
Journal Detail:
Title:  Pfl??gers Archiv : European journal of physiology     Volume:  459     ISSN:  1432-2013     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-22     Completed Date:  2010-01-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  39-46     Citation Subset:  IM    
Department of Surgery, Yale University, 310 Cedar Street, New Haven, CT 06511, USA.
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MeSH Terms
AMP-Activated Protein Kinases / drug effects,  metabolism*
Enzyme Activation / drug effects,  physiology
Enzyme Inhibitors / pharmacology
Fluorescent Antibody Technique
Gastric Acid / secretion*
Hydrogen-Ion Concentration
Mice, Inbred C57BL
Parietal Cells, Gastric / drug effects,  enzymology*,  secretion*
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; EC Protein Kinases

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