Nagtegaal J E, Siero H L, Dirksen R, Lammers J W, Rodrigues de Miranda J F, Russel F G
Department of Pharmacology, Faculty of Medical Sciences, University of Nijmegen, The Netherlands.
Life Sci. 1995;57(25):2325-33. doi: 10.1016/0024-3205(95)02227-a.
The effect of pancuronium pretreatment on the function of the prejunctional muscarinic receptor in guinea-pig trachea was studied by using electrical field stimulation (EFS). The effects of cumulative doses of the muscarinic M2 receptor antagonist gallamine were investigated in tracheal smooth muscle strips from guinea-pigs after addition of pancuronium in vitro and in strips from guinea-pigs which had been pretreated with doses of pancuronium that caused 100% neuromuscular blockade. The results of both types of experiments were compared to those of control groups of the same size. In all strips a dose response curve with cumulative doses of methacholine was made before EFS was switched on. No differences were found between the mean pD2 value and slope of the concentration-response curves of untreated guinea-pigs and animals treated with anaesthetics and pancuronium. The animals showed variable responses to pancuronium. The bath concentration of pancuronium which decreased the EFS-induced contraction to half the original value varied between 14-61 microM. The intravenous dose necessary to paralyze the muscles, varied among the different guinea-pigs from 0.017-0.085 mg.kg-1. The EFS-induced contraction for the concentration range of gallamine 0.32 microM-0.32 mM was found to differ significantly between the strips treated with pancuronium in the organ bath and their control group. For the guinea-pigs anaesthetized and pretreated with pancuronium a significant difference with control was observed at gallamine concentrations ranging from 0.032-0.32 mM. These results show that pancuronium, added to the organ bath as well as administered intravenously to the guinea-pig, masked the inhibitory muscarinic receptor.
采用电场刺激（EFS）研究了泮库溴铵预处理对豚鼠气管节前毒蕈碱受体功能的影响。在体外加入泮库溴铵后，以及在经导致100%神经肌肉阻滞剂量的泮库溴铵预处理的豚鼠的气管平滑肌条中，研究了毒蕈碱M2受体拮抗剂加拉明累积剂量的作用。将这两种实验类型的结果与相同大小的对照组的结果进行比较。在所有条带中，在开启EFS之前绘制了乙酰甲胆碱累积剂量的剂量反应曲线。未处理的豚鼠以及用麻醉剂和泮库溴铵处理的动物的浓度反应曲线的平均pD2值和斜率之间未发现差异。动物对泮库溴铵表现出不同的反应。使EFS诱导的收缩降低至原始值一半的泮库溴铵浴槽浓度在14 - 61微摩尔之间变化。使肌肉麻痹所需的静脉注射剂量在不同豚鼠之间为0.017 - 0.085毫克·千克-1。发现在器官浴中用泮库溴铵处理的条带与其对照组之间，加拉明浓度范围为0.32微摩尔 - 0.32毫摩尔时，EFS诱导的收缩存在显著差异。对于经麻醉并用泮库溴铵预处理的豚鼠，在加拉明浓度范围为0.032 - 0.32毫摩尔时观察到与对照组有显著差异。这些结果表明，添加到器官浴中以及静脉注射给豚鼠的泮库溴铵掩盖了抑制性毒蕈碱受体。
