Participation of metabotropic glutamate receptors in pentetrazol-induced kindled seizure
Participation of metabotropic glutamate receptors in pentetrazol-induced kindled seizure
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DOI：
10.1111/j.1528-1167.2010.02764.x
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发表时间：
2011-01-01
期刊：
影响因子：
5.6
通讯作者：
Kamei, Chiaki
中科院分区：
文献类型：
--
作者：
Watanabe, Yusuke;Kaida, Yuko;Kamei, Chiaki
目的：探讨代谢型谷氨酸受体（mGluR）1拮抗剂（RS）-1-氨基茚满-1，5-二羧酸（AIDA）、mGluR 2/3激动剂（2 R，4 R）-4-氨基吡咯烷-2，4-二羧酸酯（（2 R，4 R）-APDC）和mGluR 4/8激动剂L-（+）-2-氨基-4-膦酰基丁酸（L-AP 4）对戊四唑（pentrazol）点燃癫痫发作的影响。为了诱导点燃，每48小时注射一次剂量为40 mg/kg的戊四唑。行为和脑电图癫痫发作监测20分钟后，戊四唑管理。结果：侧脑室注射AIDA和L-AP 4对戊四氮点燃小鼠癫痫发作有明显的抑制作用。此外，同时使用AIDA和（2 R，4 R）-APDC或L-AP 4引起更有效的抑制癫痫发作活动。AIDA对戊四唑诱导的点燃癫痫发作的抑制作用被I组mGluR激动剂（（RS）-3，5-二羟基苯甘氨酸（（RS）-3，5-DHPG）、II组mGluR拮抗剂（2S）-α-乙基谷氨酸（EGLU）和III组mGluR拮抗剂（RS）-α-甲基-4-膦酰基苯甘氨酸（MPPG）拮抗。另一方面，L-AP 4的抑制作用被拮抗，只有MPPG。讨论：它建议，mGluR 1拮抗剂和mGluR 4/8激动剂对戊四氮诱导的点燃癫痫发作显示抗惊厥作用。此外，还提出同时使用mGluR 1拮抗剂和mGluR 2/3或mGluR 4/8激动剂是癫痫疾病的潜在新治疗策略。
P>Purpose:The present study was undertaken to clarify the effects of (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), a metabotropic glutamate receptor (mGluR) 1 antagonist, (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC), a mGluR2/3 agonist, and L-(+)-2-amino-4-phosphonobutyric acid (L-AP4), a mGluR4/8 agonist, on pentetrazol-induced kindled seizures.Methods:Mice were anesthetized with pentobarbital; the electrodes and guide cannula were chronically implanted into the cortex and lateral ventricle. To induce kindling, pentetrazol at a dose of 40 mg/kg was injected once every 48 h. Behavioral and electroencephalographic seizures were monitored for 20 min following pentetrazol administration. Fully kindled mice were used for pharmacologic studies.Results:Intracerebroventricular injection of AIDA and L-AP4 showed significant inhibitory effects on pentetrazol-induced kindled seizures. In addition, simultaneous use of AIDA and (2R,4R)-APDC or L-AP4 caused more potent inhibition of seizure activities. The inhibitory effect of AIDA on pentetrazol-induced kindled seizures was antagonized by (RS)-3,5-dihydroxyphenylglycine ((RS)-3,5-DHPG), a group I mGluR agonist; (2S)-a-ethylglutamic acid (EGLU), a group II mGluR antagonist; and (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG), a group III mGluR antagonist. On the other hand, the inhibitory effect of L-AP4 was antagonized only by MPPG.Discussion:It is proposed that mGluR1 antagonists and mGluR4/8 agonists show anticonvulsive effects on pentetrazol-induced kindled seizures. Furthermore, it is also proposed that the simultaneous use of an mGluR1 antagonist and an mGluR2/3 or mGluR4/8 agonist is a potential novel therapeutic strategy in epileptic disorders.