Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 590, Issue 14, Pages 3317-3333Publisher
WILEY
DOI: 10.1113/jphysiol.2011.226506
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Funding
- DFG [Se460/13-2, 13-4, SFB621-C9]
- German Mucoviscidosis foundation
- Lundbeck Foundation
- Karen Elise Jensens Fond
- Aarhus University Research Foundation
- Novo Nordisk Foundation
- NIH [DK050594]
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Duodenocyte pH(i) control and HCO3- secretion protects the proximal duodenum against damage by gastric acid. The molecular details of duodenocyte pH control are not well understood. A selective duodenal expression (within the upper GI tract) has been reported for the electroneutral Na+:HCO3- cotransporter NBCn1 (Slc4a7). We aimed to determine the role of NBCn1 and NBCe2 in duodenocyte intracellular pH regulation as well as basal and agonist-stimulated duodenal bicarbonate secretion (J(HCO3)(-)), exploiting mouse models of genetic slc4a7 and slc4a5 disruption. Basal and forskolin (FSK)-stimulated J(HCO3)(-) was measured by single-pass perfusion in the duodenum of slc4a7(-/-) and slc4a7(+/+) as well as slc4a5(-/-) and slc4a5(+/+) mice in vivo, and by pH-stat titration in isolated duodenal mucosa in vitro. Duodenocyte HCO3- uptake rates were fluorometrically assessed after acidification of intact villi and of isolated duodenocytes. Slc4a7(-/-) mice displayed significantly lower basal and FSK-stimulated duodenal HCO3- secretion than slc4a7(+/+) littermates in vivo. FSK-stimulated HCO3- secretion was significantly reduced in slc4a7(-/-) isolated duodenal mucosa. Na+- and HCO3--dependent base uptake rates were significantly decreased in slc4a7(-/-) compared with slc4a7(+/+) villus duodenocytes when measured in intact villi. Carbonic anhydrase (CA)-mediated CO2 hydration played no apparent role as a HCO3- supply mechanism for basal or FSK-stimulated secretion in the slc4a7(+/+) duodenum, but was an important alternative HCO3- supply mechanism in the slc4a7(-/-) duodenum. NBCe2 (Slc4a5) displayed markedly lower duodenal mRNA expression levels, and its disruption did not interfere with duodenal HCO3- secretion. The electroneutral Na+:HCO3- cotransporter NBCn1 (slc4a7) is a major duodenal HCO3- importer that supplies HCO3- during basal and FSK-stimulated HCO3- secretion.
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