| Project/Area Number |
15590638
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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 |
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)
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| Co-Investigator(Kenkyū-buntansha) |
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)
YAMAMOTO Akiko Nagoya University, 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)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | chronic pancreatitis / cystic fibrosis / CFTR / sweat chloride / interlobular pancreatic duct / Na^+-H^+ exchange / short-chain alcohol / cut-off effect / cystic fibrosis / 精密Cl^-電極 / ΔFマウス / 膵液pH / CFTR遺伝子変異 / 多型 / アルコール / 膵導管細胞 / モルモット単離小葉間膵管 / イオンチャネル / アルコール性慢性膵炎 / CFTR多型 / エタノール / 過分泌 |
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| Research Abstract |
1. Mutations and polymorphisms (TG repeats, poly T, M470V, Q1352H, R1453W) of CFTR (cystic fibrosis transmembrane conductance regulator) were examined in Japanese patients with chronic pancreatitis. None of the cystic fibrosis-causing mutations were detected. Frequency of the genotype TG(12/12) was higher in alcoholic pancreatitis. Frequency of the genotype V470/V470 was higher in idiopathic pancreatitis.
2. To estimate CFTR Cl^- channel function, we established "finger sweat chloride test" to measure Cl^- concentration in insensible sweat, which sweat is collected by holding a small tube containing 100 μl water with the thumb and the sweat rate is measured by a perspiration meter. The Cl^- content in the sample is measured by capillary electrophoresis or more easily by a highly sensitive electrode.
3. The activity of Na^+-H^+ exchange (NHE) in the apical membrane was examined in luminally-microperfused interlobular pancreatic duct segments isolated from ΔF mice, a cystic fibrosis model. The apical NHE activity significantly increased in ΔF/ΔF ducts, which may cause pH decrease of pancreatic juice.
4. Effects of a series of short-chain alcohols (methanol, ethanol, propanol, and butanol) on cAMP-stimulated fluid secretion and intracellular Ca^<2+> concentration were examined in interlobular pancreatic duct segments isolated from guinea-pig. Methanol and ethanol enhanced fluid secretion and caused a transient increase of intracellular Ca^<2+>. On the contrary, propanol and butanol inhibited fluid secretion and lowered intracellular Ca^<2+>. This "cut-off effect" suggests alcohols act directly on some ion channels of pancreatic duct cells.
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