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首页> 外文期刊>BMC Neuroscience >Convulsant bicuculline modifies CNS muscarinic receptor affinity
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Convulsant bicuculline modifies CNS muscarinic receptor affinity

机译：惊厥双小分子修饰中枢神经系统毒蕈碱受体亲和力

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Background Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP), a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl benzilate ([3H]-QNB) to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC), known to antagonize the GABA-A postsynaptic receptor subtype. Results We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg) and convulsant (7.5 mg/kg) doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity. Conclusion Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process itself. Findings support the notion that the muscarinic receptors play a major role in experimental epilepsy and provide a new example of differential neuronal plasticity.
机译：背景该实验室以前的工作表明，惊厥药物3-巯基丙酸（MP）（一种GAD抑制剂）的使用不仅可以修饰GABA的合成，还可以修饰拮抗剂[ 3 H]-苯甲酸奎宁环戊基酯（[ 3 H] -QNB）对中毒蕈碱受体，这种作用是由于亲和力增加而未改变结合位点数目所致。胆碱能系统已经牵涉到几种实验性癫痫模型中，并且乙酰胆碱调节新皮层中神经元兴奋性的能力是众所周知的。为了研究GABA能系统和胆碱能系统与癫痫发作活性之间的潜在关系，我们分析了由小瓜氨酸（BIC）诱发癫痫发作后毒蕈碱受体，已知该小拮抗剂拮抗GABA-A突触后受体亚型。结果我们分析了毒蕈碱拮抗剂[ 3 H] -QNB在腹腔镜手术后与大鼠中枢神经系统膜的结合。给予亚惊厥药（1.0 mg / kg）和惊厥药（7.5 mg / kg）剂量的BIC。惊厥性BIC剂量未能引起癫痫发作，但在小脑和海马中产生结合改变，分别增加约40％和减少10％。惊厥性BIC剂量后，总是导致全身性强直-阵挛性癫痫发作，与小脑和纹状体膜的结合分别增加36％和15％，而与海马膜的结合减少12％。因此，Kd值被修改：在亚惊厥剂量下，小脑减少27％，海马增加61％。随着惊厥剂量的增加，小脑的Kd值下降33％，海马的Kd值上升85％。没有发现受体数目位点的变化，并且希尔数目总是接近于1。结论结果表明毒蕈碱受体对BIC的中枢神经系统区域敏感性不同。配体结合不仅被惊厥性BIC剂量改变，而且还被亚惊厥性剂量改变，这表明变化不归因于癫痫发作过程本身。研究结果支持毒蕈碱受体在实验性癫痫中起主要作用的观点，并提供了差异神经元可塑性的新例子。

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