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2006 Fiscal Year Final Research Report Summary

Physiological characteristics and molecular identity of HCO_3-conductance in pancreatic duct cells.

Research Project

Project/Area Number 16590164
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionNagoya University

Principal Investigator

ISHIGURO HIROSHI  Research Center of Health, Physical Fitness, and Sports, Associate Professor, 総合保健体育科学センター, 助教授 (90303651)

Co-Investigator(Kenkyū-buntansha) KONDO TAKAHARU  Research Center of Health, Physical Fitness, and Sports, Professor, 総合保健体育科学センター, 教授 (20135388)
YAMAMOTO AKIKO  Research Center of Health, Physical Fitness, and Sports, Research Associate, 総合保健体育科学センター, 助手 (60402385)
NARUSE SATORU  Nagoya University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (50180550)
SOHMA YOSHIRO  Osaka Medical College, Lecturer, 医学部, 講師 (60268183)
Project Period (FY) 2004 – 2006
Keywordspancreatic duct cell / HCO_3^-transport / HCO_3^-conductance / Cl-HCO_3^- exchange / CFTR / SLC26A6 / sweat CI concentration / transgenic mice
Research Abstract

We have investigated molecular mechanisms for HCO_3-transport across the apical membrane of pancreatic duct cells using interlobular pancreatic duct segments isolated from guinea-pig and transgenic mice. As a clinical research, we examined polymorphisms of CFTR (cystic fibrosis transmembrane conductance regulator) in Japanese and established a simple method to measure concentration in sweat.
1. Isolated pancreatic ducts from AF mice, a cystic fibrosis model that human AF508 mutation was introduced, had very poor capacity for cAMP-stimulated fluid secretion and stronger activity of of Na^+-H^+ exchange (NHE) in the apical membrane. The enhanced of apical NHE activity may be involved in decrease of pH and acidification of pancreatic juice.
2. The HCO_3--influx mode of apical [CI^-]_i/[HCO_3^-]_o exchange was dramatically increased in slc26a6 null mice, whereas the HCO_3^--efflux mode of apical [C1^-]_i/[HCO_3^-]_o exchange was decreased in slc26a6 null mice, suggesting the uni-directionality of the slc26a6-mediated HCO_3" transport. When pure pancreatic juice was collected in vivo, neither juice volume nor its pH showed differences between WT and slc26a6 null mice.
3. The electrogenic HCO_3^-transport (HCO_3^-conductance) across the apical membrane was demonstrated in luminally-perfused isolated pancreatic ducts as changes in intracellular pH induced by manipulation of bath K^+ concentration in the condition that basolateral HCO_3^-transport was inhibited. The apical HCO_3^- conductance was not dependent on and was abolished in isolated ducts from AF mice. The data suggest that CFTR works as a HCO_3" channel in pancreatic duct cells.

  • Research Products

    (12 results)

All 2007 2006 2005

All Journal Article (12 results)

  • [Journal Article] Effect of S1c26a6 deletion on apical Cl^-/HCO_3^--exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct2007

    • Author(s)
      Ishiguro H, Namkung W, Yamamoto A, Wang Z, Worrell RT, Xu J, Lee MG, Soleimani M
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 292

      Pages: 447-455

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Is genetic analysis helpful for diagnosing chronic pancreatitis in its early stage?2007

    • Author(s)
      Naruse S, Fujiki K, Ishiguro H
    • Journal Title

      J Gastroenterol 42 Suppl17

      Pages: 60-65

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of S1c26a6 deletion on apical Cl^-/HCO_3^--exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct.2007

    • Author(s)
      Ishiguro H, et al.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol 292

      Pages: 447-455

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Is genetic analysis helpful for diagnosing chronic pancreatitis in its early stage?2007

    • Author(s)
      Naruse S, et al.
    • Journal Title

      J Gastroenterol 42 Suppl 17

      Pages: 60-65

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sweat chloride measurement with a highly sensitive electrode2006

    • Author(s)
      Naruse S, Ishiguro H, Shirota K, Nakakuki M, Yamamoto A, Kondo T
    • Journal Title

      Pancreas 33

      Pages: 100

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 膵の重炭酸イオン分泌障害と膵嚢胞線維症/慢性膵炎2006

    • Author(s)
      石黒 洋, 成瀬 達, 近藤孝晴, 山本明子
    • Journal Title

      膵臓 21(1)

      Pages: 13-25

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sweat chloride measurement with a highly sensitive electrode.2006

    • Author(s)
      Naruse S, et al.
    • Journal Title

      Pancreas 33

      Pages: 100

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dysfunction of pancreatic HCO_3^- secretion and pathogenesis of cystic fibrosis/chronic pancreatitis2006

    • Author(s)
      Ishiguro H, et al.
    • Journal Title

      J Jpn Panc Soc 21

      Pages: 13-25

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dual effects of n-alcohols on fluid secretion from guinea-pig pancreatic ducts2005

    • Author(s)
      Hamada H, Ishiguro H, Yamamoto A, Shimano-Futakuchi S, Ko SB, Yoshikawa T, Goto H, Kitagawa M, Hayakawa T, Seo Y, Naruse S
    • Journal Title

      Am J Physiol Cell Physiol 288

      Pages: C1431-C1439

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mechanisms of bicarbonate secretion in the pancreatic duct.2005

    • Author(s)
      Steward MC, Ishiguro H, Case RM
    • Journal Title

      Annu Rev Physiol 67

      Pages: 377-409

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Dual effects of n-alcohols on fluid secretion from guinea-pig pancreatic ducts.2005

    • Author(s)
      Hamada H, et al.
    • Journal Title

      Am J Physiol Cell Physiol 288

      Pages: C1431-9

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mechanisms of bicarbonate secretion in the pancreatic duct.2005

    • Author(s)
      Steward MC, et al.
    • Journal Title

      Annu Rev Physiol 67

      Pages: 377-409

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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