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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

Lookup NU author(s): Viktoria Venglovecz, Dr Georgina Carr, Professor Barry Argent, Dr Michael Gray, Dr Zoltan Rakonczay

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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 (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.

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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

Journal: Pancreas

Year: 2009

Volume: 38

Issue: 8

Pages: 921-929

ISSN (print): 0885-3177

ISSN (electronic): 1536-4828

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/MPA.0b013e3181b65d34

DOI: 10.1097/MPA.0b013e3181b65d34

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