新抗胆碱药[3H]三环哌酯对人脑M受体的作用

用放射配体受体结合试验法,研究了新化合物三环哌酯与人大脑皮质M受体的结合特性,并与QNB作了比较。饱和实验结果显示,[³H]三环哌酯的结合参数与[³H]QNB相近,两种配体的作用均符合单位点模型。竞争性抑制实验结果表明二者作用强度相当。[³H]三环哌酯的结合和解离速率常数均较[³H]QNB大,且其与皮质M受体的解离受季铵酚的变构调节,结果提示,两种配体与M受体有一些不同的结合特性,在M受体研究中,[³H]三环哌酯可以作为[³H]QNB的补充工具。

THE EFFECT OF A NEW CHOLINOLYTIC-[3H] TRICYCLOPINATE ON HUMAN BRAIN MUSCARINIC RECEPTORS

The binding characteristics of the novel cholinergic antagonist [3H] tricyclopinate with muscarinic receptors from human cerebral cortex were investigated in comparison with [3H] QNB by performing radioligand binding assays. As revealed by saturation experiments, the binding parameters of [3H] tricyclopinate (Kd = 0.044 nmol.L-1, Bmax = 514 fmol.mg-1) were almost identical with those of [3H]QNB (Kd = 0.040 nmol.L-1, Bmax = 508 fmol.mg-1). Both ligands fit a one site model of receptor-ligand interaction. Tricyclopinate showed a potency comparable to QNB on muscarinic receptors in inhibition experiments. However, some differences also existed between tricyclopinate and QNB. Kinetic experiments showed that both the association and dissociation of tricyclopinate (K1 = 1.40 (nmol.L-1)-1.min-1, K2 = 0.39 min-1) with muscarinic receptors were quicker than QNB (K1 = 0.65 (nmol.L-1)-1.min-1, K2 = 0.005 min-1). In addition, tricyclopinate behaved differently from QNB in the response of the dissociation profile to the allosteric modulation of gallamine. These results demonstrated that tricyclopinate has comparable affinity to muscarinic receptors with QNB but might interact with them in a different way. The introduction of [3H] tricyclopinate might complement the use of [3H] QNB in the study of central muscarinic receptors.