CFTR expression but not cl- transport is involved in the stimulatory effect of bile acids on apical cl-/hco3- exchange activity in human pancreatic duct cells

Imre Ignáth, Péter Hegyi, Viktória Venglovecz, Csilla A. Székely, Georgina Carr, Mamoru Hasegawa, Makoto Inoue, Tamás Takács, Barry E. Argent, Michael A. Gray, Zoltán Rakonczay

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

OBJECTIVES:: Low doses of chenodeoxycholate (CDC) stimulate apical anion exchange and HCO3 secretion in guinea pig pancreatic duct cells (Gut. 2008;57:1102-1112). We examined the effects of CDC on intracellular pH (pHi), intracellular Ca concentration ([Ca]i), and apical Cl/HCO3 exchange activity in human pancreatic duct cells and determined whether any effects were dependent on cystic fibrosis transmembrane conductance regulator (CFTR) expression and Cl channel activity. METHODS:: Polarized CFPAC-1 cells (expressing F508del CFTR) were transduced with Sendai virus constructs containing complementary DNAs for either wild-type CFTR or β-galactosidase. Microfluorimetry was used to record pHi and [Ca]i and apical Cl/HCO3 exchange activity. Patch clamp experiments were performed on isolated guinea pig duct cells. RESULTS:: Chenodeoxycholate induced a dose-dependent intracellular acidification and a marked increase in [Ca]i in CFPAC-1 cells. CFTR expression slightly reduced the rate of acidification but did not affect the [Ca]i changes. Luminal administration of 0.1 mmol/L of CDC significantly elevated apical Cl/HCO3 exchange activity but only in cells that expressed CFTR. However, CDC did not activate CFTR Cl conductance. CONCLUSIONS:: Bile salts modulate pHi, [Ca]i, and apical anion exchange activity in human pancreatic duct cells. The stimulatory effect of CDC on anion exchangers requires CFTR expression but not CFTR channel activity.

Original languageEnglish
Pages (from-to)921-929
Number of pages9
JournalPancreas
Volume38
Issue number8
DOIs
Publication statusPublished - Nov 1 2009

Keywords

  • CFTR
  • Chenodeoxycholate
  • Cl-/HCO3- exchange
  • Pancreatic duct cells
  • Sendai virus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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