权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The interaction of intravenous anesthetic agent with adrenoceptor stimulation in rat myocytes

静脉麻醉剂与大鼠肌细胞肾上腺素受体刺激的相互作用

基本信息

批准号：
14571444
负责人：
KUROKAWA Hiromi
金额：
$ 2.24万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571444/
关键词：
intravenous anesthetic agent myocyte β-signaling pathway catecholamine

项目摘要

Background : We previously reported that propofol attenuated β-adrenoreceptor-mediated signal transduction in cardiomyocytes (ASA2000, Anesthesiology 2002). Those results suggested that it is important to use propofol carefully for critically ill patients receiving catecholamines for hemodynamic support. Cyclic adenosine monophosphate (cAMP) is an important second messenger of intracellular β-adrenoreceptor-mediated signal transduction. Thus we used cAMP to investigate the effects of β-stimulant and propofol.First experiment : Olprinone, a phosphodiesterase-III inhibitor, improves poor cardiac performance by increasing cAMP level without an increase in O2 consumption. Thus, we hypothesized that olprinone could reverse the reducing effect of propofol on the isoproterenol-stimulated increase in cAMP production. Result : Olprinone reversed the attenuated production of cAMP caused by propofol on isoproterenol-stimulated cAMP production. Our results suggest that improvement of cardiac function is potentially provided by olprinone, when the β-adrenoreceptor-mediated signaling pathway is inhibited by propofol. (Anesthesiology 2004;101:A637)Second experiment : Cholera toxin (CTX) exerts an influence on G-protein by ADP-ribosylation of the stimulatory G protein alpha isoform. Thus, we investigated the effective site of action for propofol in greater detail as well as its effect on CTX-stimulated cyclic adenosine monophosphate (cAMP). Result : CTX increases cAMP by ADP-ribosylation of the stimulatory G protein alpha isoform and propofol was shown to potentiate this CTX-stimulated increase in cAMP production. Our results suggest that G protein contributes to the effective site of action for propofol. (Anesthesia & Analgesia 2005;100:S37)

背景资料：我们以前曾报道过丙泊酚减弱心肌细胞中β-肾上腺素受体介导的信号转导（ASA 2000，Anesthesiology 2002）。这些结果提示，对于接受儿茶酚胺类药物进行血流动力学支持的危重患者，应谨慎使用丙泊酚。环磷酸腺苷（cAMP）是细胞内β-肾上腺素受体介导的信号转导的重要第二信使。因此，我们使用cAMP来研究β-兴奋剂和丙泊酚的作用。第一个实验：Olprinone，一种磷酸二酯酶-III抑制剂，通过增加cAMP水平而不增加O2消耗来改善不良的心脏性能。因此，我们假设奥普力农可以逆转丙泊酚对异丙肾上腺素刺激的cAMP产生增加的减少作用。结果：奥普力农可逆转异丙酚对异丙肾上腺素刺激cAMP生成的抑制作用。我们的研究结果表明，当β-肾上腺素受体介导的信号通路被丙泊酚抑制时，奥普瑞酮可能会改善心功能。（麻醉学2004; 101：A637）第二实验：霍乱毒素（CTX）通过刺激性G蛋白α亚型的ADP-核糖基化对G蛋白产生影响。因此，我们更详细地研究了丙泊酚的有效作用部位及其对CTX刺激的环磷酸腺苷（cAMP）的影响。测试结果：CTX通过刺激性G蛋白α同种型的ADP-核糖基化增加cAMP，并且显示丙泊酚增强这种CTX刺激的cAMP产生增加。我们的研究结果表明，G蛋白有助于异丙酚的有效作用部位。（麻醉与镇痛2005;100：S37）