Document Detail

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:
PMID:  16690903     Owner:  NLM     Status:  MEDLINE    
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.
Yanfang Guan; Jin Dong; Lixuan Tackett; Jamie W Meyer; Gary E Shull; Marshall H Montrose
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-05-11
Journal Detail:
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:
Created Date:  2006-09-08     Completed Date:  2006-10-18     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G689-99     Citation Subset:  IM    
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MeSH Terms
Acids / metabolism*
Amiloride / analogs & derivatives,  pharmacology
Cation Transport Proteins / genetics,  metabolism
Colon / cytology,  drug effects,  metabolism*
Gene Expression Regulation
Membrane Proteins / genetics,  metabolism
Mice, Knockout
Sodium / metabolism*
Sodium-Hydrogen Antiporter / genetics*,  metabolism*
Grant Support
Reg. No./Substance:
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

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