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

背景：我们之前报道过异丙酚减弱心肌细胞中β-肾上腺素受体介导的信号转导（ASA2000, Anesthesiology 2002）。这些结果表明，对于接受儿茶酚胺血液动力学支持的危重患者，谨慎使用异丙酚是很重要的。环腺苷一磷酸（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，我们用cAMP来研究β-兴奋剂和异丙酚的作用。第一个实验：Olprinone，一种磷酸二酯酶- iii抑制剂，通过增加cAMP水平而不增加氧气消耗来改善心脏性能。因此，我们假设olprinone可以逆转异丙酚对异丙肾上腺素刺激的cAMP生成增加的减少作用。结果：丙泊酚对异丙肾上腺素刺激的cAMP产生有明显的抑制作用。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异丙酚抑制时，olprinone可能会改善心功能。（Anesthesiology 2004;101:A637）第二个实验：霍乱毒素（CTX）通过刺激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异丙酚的有效作用部位及其对ctx刺激的环磷酸腺苷（cAMP）的影响。结果：CTX通过刺激G蛋白α异构体的adp核糖基化增加cAMP，丙泊酚被证明可以增强CTX刺激的cAMP产生的增加。我们的结果表明，G蛋白有助于异丙酚的有效作用位点。（麻醉与镇痛2005；100:S37）

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)