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Lookup NU author(s): Viktoria Venglovecz,
Dr Georgina Carr,
Professor Barry Argent,
Dr Michael Gray,
Dr Zoltan Rakonczay
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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 (pH(i)), intracellular Ca2+ concentration ([Ca2+](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 beta-galactosidase. Microfluorimetry was used to record pH(i) and [Ca2+](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 [Ca2+](i) in CFPAC-1 cells. CFTR expression slightly reduced the rate of acidification but did not affect the [Ca2+](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 pH(i), [Ca2+](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.
Author(s): Ignáth I, Hegyi P, Venglovecz V, Székely CA, Carr G, Hasegawa M, Inoue M, Takács T, Argent BE, Gray MA, Rakonczay Z
Publication type: Article
Publication status: Published
ISSN (print): 0885-3177
ISSN (electronic): 1536-4828
Publisher: Lippincott Williams & Wilkins
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