Hidaka Ikuhiro, Kurokawa Hiromi, Yasuda Toshimichi, Hamada Hiroshi, Kawamoto Masashi, Yuge Osafumi
Department of Anesthesiology and Critical Care, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Hiroshima J Med Sci. 2009 Mar;58(1):9-15.
The effects of intravenous anesthetics on myocytes have not been fully elucidated. To investigate the effects of various intravenous anesthetics such as fentanyl, morphine, ketamine, diazepam, midazolam, thiamylal, and thiopental on the beta-adrenergic signaling pathway, we measured isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) production in freshly isolated rat ventricular myocytes. Fentanyl, morphine, ketamine, diazepam, and midazolam did not significantly affect isoproterenol-stimulated cAMP production. However, thiamylal and thiopental dose-dependently decreased cAMP production stimulated by isoproterenol or by forskolin, a direct adenylyl cyclase stimulator. In addition, we examined the role of protein kinase C (PKC) as a potential mediator of the thiamylal- or thiopental-induced effects on cAMP production using bisindolylmaleimide I, a non-specific PKC inhibitor. Bisindolylmaleimide I did not alter the inhibitory effects of thiamylal or thiopental. Thiamylal and thiopental significantly decreased isoproterenol-stimulated cAMP production by suppressing the adenylyl cyclase. We conclude that barbiturates such as thiamylal and thiopental decrease isoproterenol-stimulated cAMP production by suppressing the adenylyl cyclase through PKC-independent mechanisms.
静脉麻醉药对心肌细胞的作用尚未完全阐明。为了研究芬太尼、吗啡、氯胺酮、地西泮、咪达唑仑、硫喷妥钠和硫戊巴比妥等各种静脉麻醉药对β-肾上腺素能信号通路的影响，我们测量了在新鲜分离的大鼠心室肌细胞中异丙肾上腺素刺激的环磷酸腺苷（cAMP）生成。芬太尼、吗啡、氯胺酮、地西泮和咪达唑仑对异丙肾上腺素刺激的cAMP生成没有显著影响。然而，硫喷妥钠和硫戊巴比妥剂量依赖性地降低了异丙肾上腺素或福斯高林（一种直接的腺苷酸环化酶刺激剂）刺激的cAMP生成。此外，我们使用非特异性蛋白激酶C（PKC）抑制剂双吲哚马来酰亚胺I研究了PKC作为硫喷妥钠或硫戊巴比妥诱导的对cAMP生成影响的潜在介质的作用。双吲哚马来酰亚胺I没有改变硫喷妥钠或硫戊巴比妥的抑制作用。硫喷妥钠和硫戊巴比妥通过抑制腺苷酸环化酶显著降低了异丙肾上腺素刺激的cAMP生成。我们得出结论，硫喷妥钠和硫戊巴比妥等巴比妥类药物通过不依赖PKC的机制抑制腺苷酸环化酶，从而降低异丙肾上腺素刺激的cAMP生成。
