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Effects of bolorile anesthetics in isolated myocordial beta-adrenergic receptor transmission

bolorile 麻醉剂对离体心肌 β-肾上腺素能受体传递的影响

基本信息

批准号：
05671265
负责人：
YUGE Osafumi
金额：
$ 1.41万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

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 forskoWe conclude that sevoflurane might depress the betaAR signal transduction system by reducing ligand-receptor bindings and disrupting the relationship between the receptor and Gs.

在大鼠心肌细胞膜上研究了七氟醚对β-肾上腺素受体（β-AR）系统的影响，该系统由受体、刺激性GTP结合蛋白（Gs）和腺苷酸环化酶（AC）组成。环磷酸腺苷（cAMP）的产生速率分别由1-异丙肾上腺素、鸟苷5-O-（3-硫代三磷酸）（GTP γ S）和毛喉素刺激的cAMP产生来测量。受体研究采用二氢烯丙洛尔（[^3H] DHA）结合法进行。在1-普萘洛尔存在下测定非特异性结合。计算β AR结合能力（由最大结合位点数（Bmax）确定）和[^3H] DHA的解离常数（Kd）。通过抑制常数（Ki）来评估β AR对激动剂的亲和力，Ki是根据1-异丙肾上腺素产生[^3H] DHA结合的半数最大抑制（IC_）的浓度来计算<50>的。(1)在0-2.0mM七氟烷存在下，[^3H] DHA的Kd和1-异丙肾上腺素的Ki以浓度依赖性方式增加，而Bmax保持不变。高亲和力状态对肾上腺素受体的高和低亲和力状态的比率显着下降，从0.60 - <plus-minus>0.15至0.35 - <plus-minus>0.12。(2)在2.0 mM七氟醚浓度下，cAMP生成率<plus-minus>与1-异丙肾上腺素和<plus-minus>GTP γ S相比分别显著降低87.1 ± 4.8%和79.4 ± 7.0%，但与forsko相比无显著性差异。我们认为七氟醚可能通过减少配体-受体结合和破坏受体与Gs之间的关系来抑制β AR信号转导系统。