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.
OBJECTIVE
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(2+) concentration ([Ca(2+)]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 pHi and [Ca(2+)]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(2+)]i in CFPAC-1 cells. CFTR expression slightly reduced the rate of acidification but did not affect the [Ca(2+)]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(2+)]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.
Ignáth
Imre
I
First Department of Medicine, University of Szeged, Szeged, Hungary.
Hegyi
Péter
P
Venglovecz
Viktória
V
Székely
Csilla A
CA
Carr
Georgina
G
Hasegawa
Mamoru
M
Inoue
Makoto
M
Takács
Tamás
T
Argent
Barry E
BE
Gray
Michael A
MA
Rakonczay
Zoltán
Z
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009154:Mutation; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014162:Transfection
D001639:Bicarbonates; D002712:Chlorides; D002635:Chenodeoxycholic Acid; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002118:Calcium