Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter.

Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. Research Abstract Details 

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Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. Abstract Text:

Lara R Gawenis,Emily M Bradford,Vikram Prasad,John N Lorenz,Janet E Simpson,Lane L Clarke,Alison L Woo,Christina Grisham,L Philip Sanford,Thomas Doetschman,Marian L Miller,Gary E Shull,

The NBC1 Na+/HCO3- cotransporter is expressed in many tissues, including kidney and intestinal epithelia. NBC1 mutations cause proximal renal tubular acidosis in humans, consistent with its role in HCO3- absorption in the kidney. In intestinal and colonic epithelia, NBC1 localizes to basolateral membranes and is thought to function in anion secretion. To test the hypothesis that NBC1 plays a role in transepithelial HCO3- secretion in the intestinal tract, null mutant (NBC1-/-) mice were prepared by targeted disruption of its gene (Slc4a4). NBC1-/- mice exhibited severe metabolic acidosis, growth retardation, reduced plasma Na+, hyperal-dosteronism, splenomegaly, abnormal dentition, intestinal obstructions, and death before weaning. Intracellular pH (pH(i)) was not altered in cAMP-stimulated epithelial cells of NBC1-/- cecum, but pH(i) regulation during sodium removal and readdition was impaired. Bioelectric measurements of NBC1-/- colons revealed increased amiloride-sensitive Na+ absorption. In Ringer solution containing both Cl- and HCO3-, the magnitude of cAMP-stimulated anion secretion was normal in NBC1-/- distal colon but increased in proximal colon, with the increase largely supported by enhanced activity of the basolateral NKCC1 Na+-K+-2Cl- cotransporter. Anion substitution studies in which carbonic anhydrase was inhibited and transepithelial anion conductance was limited to HCO3- revealed a sharp decrease in both cAMP-stimulated HCO3- secretion and SITS-sensitive current in NBC1-/- proximal colon. These results are consistent with the known function of NBC1 in HCO3- absorption in the kidney and demonstrate that NBC1 activity is a component of the basolateral mechanisms for HCO3- uptake during cAMP-stimulated anion secretion in the proximal colon.

Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. Publishing Authors By Initials

LR Gawenis,EM Bradford,V Prasad,JN Lorenz,JE Simpson,LL Clarke,AL Woo,C Grisham,LP Sanford,T Doetschman,ML Miller,GE Shull,

For similar proteins: carrier proteins: membrane transport proteins: ion pumps: symporters: sodium-bicarbonate symporters research abstracts see: proteins: carrier proteins: membrane transport proteins: ion pumps: symporters: sodium-bicarbonate symporters research

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Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 9042-52

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 27

MONTH: 12

YEAR: 2006

Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. Keywords Mesh Terms:

KEYWORDS: Sodium-Bicarbonate Symporters

MESH TERMS: physiology

Chemical & Substance for Abstract: Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter. Information

Substance Name: Sodium

Registry Number: 7440-23-5

Grant and Affiliation Information for Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1 Na+/HCO3- cotransporter.

AFFILIATION: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.

Country: United States

AGENCY: United States NCRR

GRANT: T32-RR-07004

ACRONYM: RR

MEDLINETA: J Biol Chem

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