| Project/Area Number |
08671750
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | NAGASAKI UNIVERSITY |
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Principal Investigator |
SHIBATA Osamu NAGASAKI UNIVERSITY,School of Medicine Hospital, Assistant Professor, 医学部・附属病院, 助教授 (80136671)
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| Co-Investigator(Kenkyū-buntansha) |
IWANAGA Shu NAGASAKI UNIVERSITY,School of Medicine Hospital, Assistant, 医学部・附属病院, 助手 (80274661)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | phosphatidylinositol / airway smooth muscle / potassium channel opener / Kチャネル / イノシトールリン脂 |
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| Research Abstract |
Since K_<ATP> channel openers suppress the airway smooth muscle contraction, they have been investigated for the treatment of bronchial asthma. However, their potencies are different and the mechanisms involved are not fully clarified. Since there is a direct relationship between phosphatidylinositol (PI) response and airway smooth muscle contraction, we examined the effects of Y26763, a novel K_<ATP> channel opener, on PI and contractile responses of rat trachea.
The studies were conducted under guidelines approved by the Animal Care Committee. Thirty-six Male Wistar rats weighing 250-350 g were anesthetized with 50 mg/kg intraperitoneal pentobarbital and the trachea was isolated. The trachea was chopped into 3-mm-wide ring segments for the contraction, or chopped into 1-mm-wide slices for PI response with a Mcllwain tissue chopper. First, the trachea rings were suspended between stainless hooks and the resting tension was adjusted to 1.5 g. Active contraction was induced with 0.55 muM Carbachol (CCh) and 30 min later, ring relaxation was induced by stepwise cumulative additions of cromakalim or Y26763. Second, the tracheal slices were incubated with [^3H]myo-inositol and various concentrations of cromakalim or Y26763, and 15 min later the slices were incubated with 0.55 muM CCh for 60 min. The [^3H]inositol monophosphate (IP_1) formed was separated from [^3H]myo-inositol by column chromatography and counted with a liquid scintillation counter. Statistical significance (P <0.05) was determined using ANOVA.
CCh-induced tension was attenuated dose-dependently by either cromakalim or Y26763 with a significantly greater potency of Y26763. CCh-induced IP_1 accumulation was potentiated by cromakalim at a dose of 1 muM or greater, but not by Y26763.
Results show that Y26763 has a stronger effect on airway smooth muscle relaxation than cromakalim, and suggest that the difference might be accounted in part by the differential effects on PI response.
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