Effect of Slc26a6 deletion on apical Cl-/HCO3 - exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct

Hiroshi Ishiguro, Wan Namkung, Akiko Yamamoto, Zhaohui Wang, Roger T. Worrell, Jie Xu, Min Goo Lee, Manoocher Soleimani

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48 Citations (Scopus)

Abstract

The role of Slc26a6 (PAT1) on apical Cl-/HCO3 - exchange and bicarbonate secretion in pancreatic duct cells was investigated using Slc26a6 null and wild-type (WT) mice. Apical Cl -/HCO3- exchange activity was measured with the pH-sensitive dye BCECF in microperfused interlobular ducts. The HCO 3--influx mode of apical [Cl-] i/[HCO3-]o exchange (where brackets denote concentration and subscripts i and o denote intra- and extracellular, respectively) was dramatically upregulated in Slc26a6 null mice (P < 0.01 vs. WT), whereas the HCO3--efflux mode of apical [Cl -]o/[HCO3-]i exchange was decreased in Slc26a6 null mice (P < 0.05 vs. WT), suggesting the unidirectionality of the Slc26a6-mediated HCO3- transport. Fluid secretory rate in interlobular ducts were comparable in WT and Slc26a6 null mice (P > 0.05). In addition, when pancreatic juice was collected from whole animal in basal and secretin-stimulated conditions, neither juice volume nor its pH showed differences between WT and Slc26a6 null mice. Semi-quantitative RT-PCR demonstrated more than fivefold upregulation in Slc26a3 (DRA) expression in Slc26a6 knockout pancreas. In conclusion, these results point to the role of Slc26a6 in HCO3- efflux at the apical membrane and also suggest the presence of a robust Slc26a3 compensatory upregulation, which can replace the function of Slc26a6 in pancreatic ducts.

Original languageEnglish
Pages (from-to)G447-G455
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume292
Issue number1
DOIs
Publication statusPublished - 2007 Jan 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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