Document Detail


Intestinal alkaline phosphatase regulates protective surface microclimate pH in rat duodenum.
MedLine Citation:
PMID:  19451200     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Regulation of localized extracellular pH (pH(o)) maintains normal organ function. An alkaline microclimate overlying the duodenal enterocyte brush border protects the mucosa from luminal acid. We hypothesized that intestinal alkaline phosphatase (IAP) regulates pH(o) due to pH-sensitive ATP hydrolysis as part of an ecto-purinergic pH regulatory system, comprised of cell-surface P2Y receptors and ATP-stimulated duodenal bicarbonate secretion (DBS). To test this hypothesis, we measured DBS in a perfused rat duodenal loop, examining the effect of the competitive alkaline phosphatase inhibitor glycerol phosphate (GP), the ecto-nucleoside triphosphate diphosphohydrolase inhibitor ARL67156, and exogenous nucleotides or P2 receptor agonists on DBS. Furthermore, we measured perfusate ATP concentration with a luciferin-luciferase bioassay. IAP inhibition increased DBS and luminal ATP output. Increased luminal ATP output was partially CFTR dependent, but was not due to cellular injury. Immunofluorescence localized the P2Y(1) receptor to the brush border membrane of duodenal villi. The P2Y(1) agonist 2-methylthio-ADP increased DBS, whereas the P2Y(1) antagonist MRS2179 reduced ATP- or GP-induced DBS. Acid perfusion augmented DBS and ATP release, further enhanced by the IAP inhibitor l-cysteine, and reduced by the exogenous ATPase apyrase. Furthermore, MRS2179 or the highly selective P2Y(1) antagonist MRS2500 co-perfused with acid induced epithelial injury, suggesting that IAP/ATP/P2Y signalling protects the mucosa from acid injury. Increased DBS augments IAP activity presumably by raising pH(o), increasing the rate of ATP degradation, decreasing ATP-mediated DBS, forming a negative feedback loop. The duodenal epithelial brush border IAP-P2Y-HCO(3-) surface microclimate pH regulatory system effectively protects the mucosa from acid injury.
Authors:
Misa Mizumori; Maggie Ham; Paul H Guth; Eli Engel; Jonathan D Kaunitz; Yasutada Akiba
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-05-18
Journal Detail:
Title:  The Journal of physiology     Volume:  587     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-15     Completed Date:  2009-10-15     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  3651-63     Citation Subset:  IM    
Affiliation:
Department of Medicine, School of Medicine, University of California Los Angeles, CA 90073, USA.
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MeSH Terms
Descriptor/Qualifier:
Alkaline Phosphatase / metabolism*
Animals
Carbonates / chemistry,  metabolism*
Duodenum / chemistry*,  metabolism*
Epithelial Cells / chemistry*,  metabolism*
Hydrogen-Ion Concentration
Intestinal Mucosa / chemistry*,  metabolism*
Male
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
P30 DK0413/DK/NIDDK NIH HHS; R01DK54221/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Carbonates; EC 3.1.3.1/Alkaline Phosphatase
Comments/Corrections
Comment In:
J Physiol. 2009 Jul 15;587(Pt 14):3409   [PMID:  19602628 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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