| Title | PAT-1 (Slc26a6) is the Predominant Apical Membrane Cl-/HCO3- Exchanger in the Upper Villous Epithelium of Murine Duodenum. | | Author(s) | Simpson JE, Schweinfest C, Shull GE, Gawenis L, Walker NM, Boyle KT, Soleimani M, Clarke LL | | Institution | Biomed Sci, University of Missouri-Columbia, Columbia, Missouri, United States; Veterinary Pathobiology, University of Missouri-Columbia, Columbia, Missouri, United States. | | Source | Am J Physiol Gastrointest Liver Physiol 2006 Dec 14. | | Abstract | Basal HCO3(-) secretion across the duodenum has been shown in several species to principally involve the activity of apical membrane Cl(-)/HCO3(-) exchanger(s). To investigate the identity of relevant anion exchanger(s), studies were performed using wild-type (WT) mice and mice with gene-targeted deletion of Cl(-)/HCO3(-) exchangers localized to the apical membrane of murine duodenal villi: Slc26a3 (down-regulated in adenoma, DRA); Slc26a6 (putative anion transporter-1, PAT-1); and Slc4a9 (anion exchanger 4, AE4). RT-PCR of isolated villous epithelium demonstrated PAT-1, DRA, and AE4 mRNA expression. Using the pH-sensitive dye BCECF, anion exchange rates were measured across the apical membrane of epithelial cells in the upper villus of intact duodenal mucosa. Under basal conditions, Cl(-)/HCO3(-) exchange activity was reduced by 65-80% in PAT-1 (-), 30-40% in the DRA (-), and <5% in the AE4 (-) duodena as compared to WT. SO4(2-)/HCO3(-) exchange was eliminated in the PAT-1 (-) but not affected in the DRA (-) and AE4 (-) duodena relative to WT. Intracellular pH (pHi) was reduced in the PAT-1(-) villous epithelium but increased to WT levels in the absence of CO2/HCO3(-) or during methazolamide treatment. Further studies under physiological conditions indicated active pHi compensation in the PAT-1(-) villous epithelium by conbined activities of the Na(+)/H(+) exchanger NHE1 and Cl(-)-dependent transport processes at the basolateral membrane. We conclude that 1) PAT-1 is the major contributor to basal Cl(-)/HCO3(-) and SO4(2-)/HCO3(-) exchange across the apical membrane and 2) PAT-1 plays a role in pHi regulation in the upper villous epithelium of murine duodenum. Key words: Slc26a3, down regulated in adenoma, Slc4a9, anion exchanger 4, intestine. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 17170027 |
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