Scholz J, Tonner P H, Krause T, Paris A, Steinfath M, Wappler F, von Knobelsdorff G
Klinik für Anästhesiologie, Universitäts-Krankenhaus Eppendorf, Hamburg.
Anasthesiol Intensivmed Notfallmed Schmerzther. 1999 Oct;34(10):642-7. doi: 10.1055/s-1999-219.
Up to date the exact mechanisms of action of anaesthetics on structures of the central nervous system have not been elucidated. Agents acting on central alpha 2-adrenoceptors have been demonstrated to possess potent sedative properties. Beside the classical agonists, general anaesthetics that are currently in clinical use e.g. etomidate have also been shown to act on alpha 2-adrenoceptors. Thus, the aim of this study was to study the effect of the intravenous anaesthetic agents propofol and ketamine on the binding of the specific alpha 2-adrenoceptor agonist paraiodoclonidine at cerebral alpha 2 adrenoceptors.
After approval of the local animal care committee brain tissue of six Wistar rats was removed and frozen at -80 degrees C. The tissue was sectioned in 15-20 microns thick slices. After washing in TRIS-buffer (pH = 7.5) the slices were incubated with 2.5 nM 125I-paraiodoclonidine (PIC) for determination of specific binding. Unspecific binding was determined in presence of 200 microM unlabeled clonidine. Displacement experiments were performed in presence of propofol (11-530 microM) and ketamine (52-1100 microM) and evaluated autoradiographically. Average exposure time was three days. All films were then analysed by densitometry. Statistical significance calculated by Student's t-test was assumed at a level of p < 0.05.
Only at the highest concentration of propofol and ketamine an effect on PIC binding was noticeable. Neither propofol nor ketamine was able to displace PIC completely from cerebral alpha 2-adrenoceptors.
In contrast to other anaesthetics such as etomidate which was demonstrated to displace PIC completely from alpha 2-adrenoceptors, propofol and ketamine exerted only minor effects on the binding of PIC even at concentrations that exceeded clinical concentrations. These data suggest that an additional site of action of these anaesthetics at cerebral alpha 2-adrenoceptors beside the known actions on GABA receptors or NMDA receptors is unlikely.
迄今为止，麻醉药对中枢神经系统结构的确切作用机制尚未阐明。已证明作用于中枢α2-肾上腺素能受体的药物具有强效镇静特性。除了经典激动剂外，目前临床使用的全身麻醉药如依托咪酯也已显示出作用于α2-肾上腺素能受体。因此，本研究的目的是研究静脉麻醉药丙泊酚和氯胺酮对特异性α2-肾上腺素能受体激动剂对碘氯苯胍在脑α2-肾上腺素能受体上结合的影响。
经当地动物护理委员会批准后，取出6只Wistar大鼠的脑组织并在-80℃下冷冻。将组织切成15-20微米厚的切片。在TRIS缓冲液（pH = 7.5）中洗涤后，将切片与2.5 nM 125I-对碘氯苯胍（PIC）一起孵育以测定特异性结合。在存在200μM未标记可乐定的情况下测定非特异性结合。在存在丙泊酚（11-5³0μM）和氯胺酮（52-1100μM）的情况下进行置换实验，并通过放射自显影进行评估。平均曝光时间为三天。然后通过光密度测定法分析所有胶片。采用Student's t检验计算的统计学显著性设定为p <0.05。
仅在丙泊酚和氯胺酮的最高浓度下，对PIC结合的影响才明显。丙泊酚和氯胺酮均不能将PIC从脑α2-肾上腺素能受体上完全置换下来。
与其他麻醉药如依托咪酯（已证明可将PIC从α2-肾上腺素能受体上完全置换下来）不同，丙泊酚和氯胺酮即使在超过临床浓度的情况下，对PIC结合的影响也很小。这些数据表明，除了已知的对GABA受体或NMDA受体的作用外，这些麻醉药在脑α2-肾上腺素能受体上不太可能存在其他作用位点。
