| Project/Area Number |
05671265
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
YUGE Osafumi Hiroshima Univ.School of Medicine Prof., 医学部, 教授 (40034128)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAO Masakazu Hiroshima Univ.School of Medicine Research Associate, 医学部, 助手 (90164128)
YAMANOUE Takao Hiroshima Univ.School of Medicine Research Associate, 医学部, 助手 (10174765)
FUJII Kohyu Hiroshima Univ.School of Medicine Associate Prof., 医学部, 講師 (60034021)
KAWAMOTO Masashi Hiroshima Univ.School of Medicine Associate Prof., 医学部, 助教授 (40127642)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | GTP binding protein / Beta-adrenoceptor / Adenyl cyclase / Sevoflurane / GTPgammaS / c-AMP / Bmax / Kd / C-AMP / 揮発性吸入麻酔薬 / 心室筋 / β-アドレナリン受容体-共役系 / G蛋白質 / アデニル酸シクラーゼ / GTPアナログ / フォルスコリン / アデニル酸シクラーゼ活性 / GTPγS |
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| Research Abstract |
The effects of sevoflurane on the beta-adrenoceptor (betaAR) system consisting of the receptor, stimulatory GTP binding protein (Gs) , and adenylate cyclase (AC) , were studied in rat myocardial membrane. Cyclic adenosine monophosphate (cAMP) production rate was measured as cAMP generation stimulated by 1-isoproterenol, guanosine 5-O- (3-thiotriphoshate) (GTPgammaS) and forskolin, repectively. The receptor studies were carried out by using the dihydroalprenolol ( [^3H] DHA) binding method. Non-specific binding was determined in the presence of 1-propranolol. betaAR binding capacity determined by the maximal number of binding sites (Bmax) and the dissociation constant (Kd) for [^3H] DHA were calculated. betaAR affinity for agonists was assessed by an inhibition constant (Ki) , which was calculated from the concentration of 1-isoproterenol to produce half-maximal inhibition of [^3H] DHA binding (IC_<50>).
(1) In the presence of 0-2.0mM sevoflurane, Kd for [^3H] DHA and Ki for 1-isoproterenol increased in a concentration-dependent manner, while Bmax remained unchanged. The ratio of high affinity state against the high and low affinity state of the adrenoceptor decreased significantly from 0.60 <plus-minus> 0.15 to 0.35 <plus-minus> 0.12.
(2) At 2.0 mM sevoflurane concentration, cAMP production rate was significantly depressed by 87.1 <plus-minus> 4.8% with 1-isoproterenol and by 79.4 <plus-minus> 7.0% with GTPgammaS,but not significantly depressed by forsko
We conclude that sevoflurane might depress the betaAR signal transduction system by reducing ligand-receptor bindings and disrupting the relationship between the receptor and Gs.
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