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II 型代谢型谷氨酸受体激动剂LY354740和DCG-IV的突触前抑制作用

Presynaptic inhibitory action of the group II metabotropic glutamate receptor agonists, LY354740 and DCG-IV.

作者信息

Kilbride J, Huang L Q, Rowan M J, Anwyl R

机构信息

Department of Physiology, Trinity College, Dublin, Ireland.

出版信息

Eur J Pharmacol. 1998 Sep 4;356(2-3):149-57. doi: 10.1016/s0014-2999(98)00526-3.

DOI:10.1016/s0014-2999(98)00526-3
PMID:9774244
Abstract

Electrophysiological studies were carried out on the presynaptic inhibitory action of the group II metabotropic glutamate (mGlu) receptor agonists (+)-2-aminobicyclo[3.1.0]hexane-2-6-dicarboxylic acid (LY354740) and (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) in three paths of the rat hippocampus, the medial and lateral perforant path to the dentate gyrus, and the Schaffer collateral/commissural path to CA1. LY354740 caused a dose-dependent reversible inhibition of the field excitatory postsynaptic potential (EPSP) in the medial and lateral perforant paths, with an EC50 of 115 +/- 16 nM and 230 +/- 58 nM, respectively. Maximal inhibition by LY354740 was much greater in the medial path (about 80%) than in the lateral path (about 50%). No inhibition was observed in CA1. A presynaptic inhibition was confirmed by LY354740 inducing dose-dependent changes in paired-pulse depression/facilitation. DCG-IV had a similar action to LY354740, but with a lower potency.

摘要

对大鼠海马三条通路,即至齿状回的内侧和外侧穿通通路以及至CA1的Schaffer侧支/连合通路,开展了关于II型代谢型谷氨酸(mGlu)受体激动剂(+)-2-氨基双环[3.1.0]己烷-2,6-二羧酸(LY354740)和(2S,1'R,2'R,3'R)-2-(2',3'-二羧基环丙基)甘氨酸(DCG-IV)的突触前抑制作用的电生理研究。LY354740对内侧和外侧穿通通路中的场兴奋性突触后电位(EPSP)产生剂量依赖性的可逆抑制,其EC50分别为115±16 nM和230±58 nM。LY354740在内侧通路中的最大抑制作用(约80%)远大于外侧通路(约50%)。在CA1中未观察到抑制作用。LY354740诱导成对脉冲抑制/易化的剂量依赖性变化,证实了存在突触前抑制。DCG-IV具有与LY354740相似的作用,但效力较低。

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