| NHE2 is the main apical NHE in mouse colonic crypts but an alternative Na+-dependent acid extrusion mechanism is upregulated in NHE2-null mice. | |
MedLine Citation:
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PMID: 16690903 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanism of apical Na(+)-dependent H(+) extrusion in colonic crypts is controversial. With the use of confocal microscopy of the living mouse distal colon loaded with BCECF or SNARF-5F (fluorescent pH sensors), measurements of intracellular pH (pH(i)) in epithelial cells at either the crypt base or colonic surface were reported. After cellular acidification, the addition of luminal Na(+) stimulated similar rates of pH(i) recovery in cells at the base of distal colonic crypts of wild-type or Na(+)/H(+) exchanger isoform 2 (NHE2)-null mice. In wild-type crypts, 20 microM HOE694 (NHE2 inhibitor) blocked 68-75% of the pH(i) recovery rate, whereas NHE2-null crypts were insensitive to HOE694, the NHE3-specific inhibitor S-1611 (20 microM), or the bicarbonate transport inhibitor 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS; 1 mM). A general NHE inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA; 20 microM), inhibited pH(i) recovery in NHE2-null mice (46%) but less strongly than in wild-type mice (74%), suggesting both EIPA-sensitive and -insensitive compensatory mechanisms. Transepithelial Na(+) leakage followed by activation of basolateral NHE1 could confound the outcomes; however, the rates of Na(+)-dependent pH(i) recovery were independent of transepithelial leakiness to lucifer yellow and were unchanged in NHE1-null mice. NHE2 was immunolocalized on apical membranes of wild-type crypts but not NHE2-null tissue. NHE3 immunoreactivity was near the colonic surface but not at the crypt base in NHE2-null mice. Colonic surface cells from wild-type mice demonstrated S1611- and HOE694-sensitive pH(i) recovery in response to luminal sodium, confirming a functional role for both NHE3 and NHE2 at this site. We conclude that constitutive absence of NHE2 results in a compensatory increase in a Na(+)-dependent, EIPA-sensitive acid extruder distinct from NHE1, NHE3, or SITS-sensitive transporters. |
Authors:
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Yanfang Guan; Jin Dong; Lixuan Tackett; Jamie W Meyer; Gary E Shull; Marshall H Montrose |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-05-11 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 291 ISSN: 0193-1857 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-08 Completed Date: 2006-10-18 Revised Date: 2014-09-14 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G689-99 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acids
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metabolism* Amiloride / analogs & derivatives, pharmacology Animals Cation Transport Proteins / genetics, metabolism Colon / cytology, drug effects, metabolism* Gene Expression Regulation Membrane Proteins / genetics, metabolism Mice Mice, Knockout Sodium / metabolism* Sodium-Hydrogen Antiporter / genetics*, metabolism* Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK042457/DK/NIDDK NIH HHS; R01-DK-42457/DK/NIDDK NIH HHS; R01-DK-50594/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Acids; 0/Cation Transport Proteins; 0/Membrane Proteins; 0/Slc9a1 protein, mouse; 0/Slc9a2 protein, mouse; 0/Sodium-Hydrogen Antiporter; 0/sodium-hydrogen exchanger 3; 1154-25-2/ethylisopropylamiloride; 7DZO8EB0Z3/Amiloride; 9NEZ333N27/Sodium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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