| Project/Area Number |
16590164
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Nagoya University |
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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)
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| 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)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | pancreatic duct cell / HCO_3^-transport / HCO_3^-conductance / Cl-HCO_3^- exchange / CFTR / SLC26A6 / sweat CI concentration / transgenic mice / Cl^--HCO_3^- exchange / Na^+-H^+ exchange / cystic fibrosis / 単離小葉間膵管 / 短鎖アルコール / cut-off effect / 管腔膜 / モルモット単離小葉間膵管 / アルコール / 慢性膵炎 |
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| 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.
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