Hirota K, Lambert D G
University Department of Anaesthesia, Leicester Royal Infirmary.
Br J Anaesth. 1996 Sep;77(3):385-6. doi: 10.1093/bja/77.3.385.
In this study we have examined if the i.v. anaesthetic agents thiopentone, pentobarbitone, ketamine, etomidate, propofol and alphaxalone interact with the verapamil binding site on L-type voltage-sensitive Ca2+ channels in rat cerebrocortical membranes. Binding assays were performed in 1 ml volumes of Tris HCl 50 mmol litre-1, pH 7.4, for 90 min at 20 degrees C, with cerebrocortical membranes (200 micrograms of protein), the verapamil binding sites of which were radiolabelled with [3H]verapamil. Non-specific binding was defined in the presence of verapamil 10(-6) mol litre-1. The interaction of i.v. anaesthetics was determined by displacement of [3H]verapamil 0.2 nmol litre-1. The mean concentrations of anaesthetic producing 25% inhibition of specific binding (corrected for the competing mass of [3H]verapamil), K25, were (mmol litre-1): thiopentone 0.68 (SEM 0.14); pentobarbitone 1.22 (0.13); propofol 0.66 (0.10); etomidate 0.24 (0.03); alphaxalone 0.19 (0.02); and ketamine 0.75 (0.04). These concentrations exceeded those seen during anaesthesia and suggest that the neuronal verapamil binding site may not be an important target for i.v. anaesthetic agents.
在本研究中，我们检测了静脉麻醉药硫喷妥钠、戊巴比妥、氯胺酮、依托咪酯、丙泊酚和阿法沙龙是否与大鼠大脑皮质膜中L型电压敏感性Ca2+通道上的维拉帕米结合位点相互作用。结合试验在50 mmol/L Tris HCl（pH 7.4）1 ml体积中于20℃进行90分钟，使用大脑皮质膜（200μg蛋白质），其维拉帕米结合位点用[3H]维拉帕米进行放射性标记。非特异性结合在10-6 mol/L维拉帕米存在下定义。静脉麻醉药的相互作用通过0.2 nmol/L [3H]维拉帕米的置换来确定。产生特异性结合25%抑制（校正[3H]维拉帕米的竞争质量）的麻醉药平均浓度K25为（mmol/L）：硫喷妥钠0.68（标准误0.14）；戊巴比妥1.22（0.13）；丙泊酚0.66（0.10）；依托咪酯0.24（0.03）；阿法沙龙0.19（0.02）；氯胺酮0.75（0.04）。这些浓度超过了麻醉期间所见浓度，提示神经元维拉帕米结合位点可能不是静脉麻醉药的重要作用靶点。
