| AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion. | |
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MedLine Citation:
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PMID: 19621238 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Shafik Sidani; Sascha Kopic; Thenral Socrates; Philipp Kirchhoff; Michael F??ller; Michael Murek; Anna Capasso; John P Geibel |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-07-21 |
Journal Detail:
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Title: Pfl??gers Archiv : European journal of physiology Volume: 459 ISSN: 1432-2013 ISO Abbreviation: Pflugers Arch. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-22 Completed Date: 2010-01-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0154720 Medline TA: Pflugers Arch Country: Germany |
Other Details:
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Languages: eng Pagination: 39-46 Citation Subset: IM |
Affiliation:
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Department of Surgery, Yale University, 310 Cedar Street, New Haven, CT 06511, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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drug effects,
metabolism* Animals Enzyme Activation / drug effects, physiology Enzyme Inhibitors / pharmacology Fluorescent Antibody Technique Gastric Acid / secretion* Hydrogen-Ion Concentration Mice Mice, Inbred C57BL Parietal Cells, Gastric / drug effects, enzymology*, secretion* |
| Grant Support | |
ID/Acronym/Agency:
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DK07017-29/DK/NIDDK NIH HHS; DK17433/DK/NIDDK NIH HHS; DK50230/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; EC 2.7.11.1/AMP-Activated Protein Kinases |
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