| Project/Area Number |
13670506
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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 |
Gastroenterology
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| Research Institution | Nagoya University |
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Principal Investigator |
ISHIGURO Hiroshi Nagoya University, 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) |
KITAGAWA Motoji Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (80262898)
NARUSE Satoru Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (50180550)
KONDO Takaharu Nagoya University, Research Center of Health, Physical Fitness and Sports, Professor, 総合保健体育科学センター, 教授 (20135388)
HAYAKAWA Tetsuo Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80022838)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | pancreatic duct / bicarbonate ion / membrane potential / CFTR / sodium-bicarbonate cotransport / 膵導管細胞 / イオン・水輸送 / エタノール / CFTR多型 / アルコール性慢性膵炎 / HCO_3^-分泌 / 単離小葉間膵管 / 電気化学勾配 / 細胞内電位 / 重炭酸イオンチャネル / Na^+-HCO_3^-共輸送体 / セクレチン / 細胞内Cl^-濃度 / 5-hydroxytriptamine / Na^+-HCO_3^-cotransport / 水チャネル |
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| Research Abstract |
The interlobular duct cells of the guinea-pig pancreas secrete HCO_3^-across their luminal membrane into a HCO_3^--rich (125 mM) luminal fluid against a six-fold concentration gradient. Since HCO_3^-transport cannot be achieved by luminal Cl^-/HCO_3^-exchange under these conditions, we have investigated the possibility that it is mediated by an anion conductance. We have measured intracellular pH (HCO_3^-concentration, [HCO_3^-]_i) and Cl^-concentration ([CO^-]_i) by microfluorometry (using BCECF and MEQ) and the intracellular potential (Vm) by microelectrode of duct cells in luminally-microperfused, interlobular duct segments. When the lumen was perfused with a high HCO_3^-(24 mM CL^--125 mM HCO_3^-) solution (to simulate physiological condition in vivo) under cAMP stimulation, [HCO_3^-]_i was at 〜20 mM, [Cl^-]_i was as little as 〜7 mM, and V_m was 〜-60 mV. These results can be explained by a model in which the depolarizing effect of Cl^-efflux via CFTR across the luminal membrane is minimized by the depletion of intracellular Cl^-and offset by the hyperpolarizing effects of electrogenic Na^+-HCO_3^-cotransport (stoichiometry=1:2) at the basolateral membrane. The net effect is a luminally directed electrochemical potential gradient for HCO_3^-that is sustained during maximal stimulation. Our calculations indicate that the electrodiffusive efflux of HCO_3^-to the lumen via CFTR, driven by this gradient, would be sufficient to fully account for the observed secretory flux of HCO_3^-.
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