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, P. Hegyi, V. Venglovecz, Csilla A. Székely, Georgina Carr, Mamoru Hasegawa, Makoto Inoue, T. Takács, Barry E. Argent, Michael A. Gray, Z. 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 2009

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Cystic Fibrosis Transmembrane Conductance Regulator
Pancreatic Ducts
Bile Acids and Salts
Chenodeoxycholic Acid
Human Activities
Anions
Guinea Pigs
Galactosidases
Cytophotometry
Sendai virus
Complementary DNA

Keywords

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

ASJC Scopus subject areas

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

Cite this

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. / Ignáth, Imre; Hegyi, P.; Venglovecz, V.; Székely, Csilla A.; Carr, Georgina; Hasegawa, Mamoru; Inoue, Makoto; Takács, T.; Argent, Barry E.; Gray, Michael A.; Rakonczay, Z.

In: Pancreas., Vol. 38, No. 8, 11.2009, p. 921-929.

Research output: Contribution to journalArticle

Ignáth, Imre ; Hegyi, P. ; Venglovecz, V. ; Székely, Csilla A. ; Carr, Georgina ; Hasegawa, Mamoru ; Inoue, Makoto ; Takács, T. ; Argent, Barry E. ; Gray, Michael A. ; Rakonczay, Z. / 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. In: Pancreas. 2009 ; Vol. 38, No. 8. pp. 921-929.
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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 (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.",
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TY - JOUR

T1 - 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

AU - Ignáth, Imre

AU - Hegyi, P.

AU - Venglovecz, V.

AU - Székely, Csilla A.

AU - Carr, Georgina

AU - Hasegawa, Mamoru

AU - Inoue, Makoto

AU - Takács, T.

AU - Argent, Barry E.

AU - Gray, Michael A.

AU - Rakonczay, Z.

PY - 2009/11

Y1 - 2009/11

N2 - 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.

AB - 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.

KW - CFTR

KW - Chenodeoxycholate

KW - Cl-/HCO3- exchange

KW - Pancreatic duct cells

KW - Sendai virus

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DO - 10.1097/MPA.0b013e3181b65d34

M3 - Article

VL - 38

SP - 921

EP - 929

JO - Pancreas

JF - Pancreas

SN - 0885-3177

IS - 8

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