In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 292, No. 4 ( 2007-04), p. G1079-G1088
Abstract:
Basal HCO 3 − secretion across the duodenum has been shown in several species to principally involve the activity of apical membrane Cl − /HCO 3 − exchanger(s). To investigate the identity of relevant anion exchanger(s), experiments were performed using wild-type (WT) mice and mice with gene-targeted deletion of the following Cl − /HCO 3 − 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 the 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 the intact duodenal mucosa. Under basal conditions, Cl − /HCO 3 − exchange activity was reduced by 65–80% in the PAT-1(−) duodenum, 30–40% in the DRA(−) duodenum, and 〈 5% in the AE4(−) duodenum compared with the WT duodenum. SO 4 2− /HCO 3 − exchange was eliminated in the PAT-1(−) duodenum but was not affected in the DRA(−) and AE4(−) duodenum relative to the WT duodenum. Intracellular pH (pH i ) was reduced in the PAT-1(−) villous epithelium but increased to WT levels in the absence of CO 2 /HCO 3 − or during methazolamide treatment. Further experiments under physiological conditions indicated active pH i compensation in the PAT-1(−) villous epithelium by combined activities of Na + /H + exchanger 1 and Cl − -dependent transport processes at the basolateral membrane. We conclude that 1) PAT-1 is the major contributor to basal Cl − /HCO 3 − and SO 4 2− /HCO 3 − exchange across the apical membrane and 2) PAT-1 plays a role in pH i regulation in the upper villous epithelium of the murine duodenum.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.00354.2006
Language:
English
Publisher:
American Physiological Society
Publication Date:
2007
detail.hit.zdb_id:
1477329-6
SSG:
12
