Effects of subtype-selective group I mGluR antagonists on synchronous activity induced by 4-aminopyridine/CGP 55845 in adult guinea pig hippocampal slices.
Effects of subtype-selective group I mGluR antagonists on synchronous activity induced by 4-aminopyridine/CGP 55845 in adult guinea pig hippocampal slices.
复制标题
亚型选择性 I 组 mGluR 拮抗剂对 4-氨基吡啶/CGP 55845 诱导的成年豚鼠海马切片同步活性的影响。
DOI：
10.1016/j.neuropharm.2008.04.010
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发表时间：
2008
影响因子：
4.7
通讯作者：
Perkins,KatherineL
中科院分区：
文献类型：
--
作者：
Salah,Alejandro;Perkins,KatherineL
将惊厥剂4-氨基吡啶（4-AP）和GABAB受体拮抗剂CGP 55845共同应用于成年豚鼠海马脑片，引发巨大的GABA介导的突触后电位（GPSP）和癫痫样放电。在这里，我们测试了I组代谢型谷氨酸受体（mGluR）亚型选择性拮抗剂LY 367385（mGlu 1，100μM）、MPEP（mGlu 5，10μM）和MTEP（mGlu 5，500 nM）对这种同步活性的影响。在成年豚鼠海马脑片的CA 3区进行电生理场记录。mGlu 5受体拮抗剂增加GPSP率，而mGlu 1受体拮抗剂不增加。mGlu 5受体拮抗剂增加GPSP速率的能力表明，在这些条件下释放了足够的内源性谷氨酸盐以激活I组mGluR;然而，mGlu 1受体拮抗剂（LY 367385或JNJ 16259685）和MPEP联合给药并未降低既存癫痫样活动。此外，LY 367385和MPEP的联合应用不能预防癫痫样活动的出现。当存在离子型谷氨酸受体（iGluR）拮抗剂时，MPEP和I组mGluR激动剂DHPG都没有改变GPSP速率，这表明锥体细胞与中间神经元iGluR介导的突触连接参与了速率变化机制。与I组mGluR拮抗剂对4-AP/CGP 55845模型中癫痫样活动缺乏作用相反，I组mGluR拮抗剂阻断了GABA A拮抗剂/4-AP模型中较长癫痫样事件的出现并降低了同步活动的总量。总之，在4-AP/CGP 55845模型中，释放了足够的谷氨酸以激活I组mGluR并通过mGlu 5受体影响GPSP速率;然而，I组mGluR激活不是产生癫痫样活性所必需的。
Co-application of the convulsant 4-aminopyridine (4-AP) and the GABABreceptor antagonist CGP 55845 to adult guinea pig hippocampal slices elicits giant GABA-mediated postsynaptic potentials (GPSPs) and epileptiform discharges. Here we tested the effects of the group I metabotropic glutamate receptor (mGluR) subtype-selective antagonists LY 367385 (mGlu1, 100μM), MPEP (mGlu5, 10μM), and MTEP (mGlu5, 500nM) on this synchronous activity. Electrophysiological field recordings were performed in the CA3 region of hippocampal slices from adult guinea pigs. The mGlu5 receptor antagonists increased GPSP rate, but the mGlu1 receptor antagonist did not. This ability of mGlu5 receptor antagonists to increase the rate of GPSPs indicates that enough endogenous glutamate is released under these conditions to activate group I mGluR; nevertheless, co-application of a mGlu1 receptor antagonist (LY 367385 or JNJ 16259685) and MPEP did not decrease pre-existing epileptiform activity. Furthermore, co-application of LY 367385 and MPEP did not prevent the emergence of epileptiform activity. When ionotropic glutamate receptor (iGluR) antagonists were present, neither MPEP nor the group I mGluR agonist DHPG changed GPSP rate, suggesting that pyramidal cell-to-interneuron iGluR-mediated synaptic connections are involved in the rate change mechanism. In contrast to the lack of effect of group I mGluR antagonists on epileptiform activity in the 4-AP/CGP 55845 model, group I mGluR antagonists blocked the emergence of longer epileptiform events and decreased the overall amount of synchronous activity in the GABAAantagonist/4-AP model. In conclusion, in the 4-AP/CGP 55845 model, enough glutamate was released to activate group I mGluRs and affect GPSP rate via mGlu5 receptors; however, this group I mGluR activation was not required for the generation of the epileptiform activity.