Basic research on metabotropic glutamate receptors and neural plasticity.

基于代谢型谷氨酸受体、使君子酸启动和神经可塑性之间存在正相关的观点，我们研究了代谢型谷氨酸受体激动剂诱导的启动，发现AMPB [L-2-amino-4-（甲基膦基）丁酸]与使君子酸引发有关，而L-F2CCG-I [2S，1'S，2'S）-2-（2-羧基-3，3-二氟环丙基）甘氨酸]在引起2-（2-（2-（2-羧基-3，3-二氟环丙基）甘氨酸）的8种立体异构体中的去极化方面是最有效的（基于摩尔）。（2-羧基-3，3-二氟环丙基）甘氨酸，阈值浓度约为1 μ M（10- 30 μ M）可被MCPG（1 mM）有效地抑制，而仅被高浓度的D-AP 5（100 μ M）轻微降低，但不被CNQX（100 μ M）所抑制，表明L-F_2CCG-I激活代谢型谷氨酸受体。L-F_2CCG-I优先抑制脊髓反射的单突触成分，其抑制效果是（2S， ...更多信息 1 ′ S，2 ′ S）-2-（羧基-环丙基）甘氨酸（L-CCG-I）。L-F_2CCG-Ⅰ（0.2 μ M-0.7 μ M）对单突触兴奋的抑制作用可被MCCG（0.3mM-1 mM）和MAP_4（0.3mM）有效地阻断。DL-α-氨基庚二酸，浓度低于0.1 mM（阈值浓度：3 μ M），选择性地增强L-CCG-I、L-F_2CCG-I和L-F_2CCG-I对单突触兴奋的抑制作用，（2S，1'S，2'R，3'S）-2-（2-羧基-3-甲氧基甲基环丙基）甘氨酸（trans-MCG-I），但（2S，1'R，2'R，3'R）-2-（2，3-二羧基环丙基）甘氨酸（DCG-IV），L-AP 4，（1 S，DL-α-aminopimelic acid对L-F_2CCG-I的抑制作用不明显，而对L-F_2CCG-I的抑制作用不明显。（如30 μ M）、DL-α-氨基庚二酸和羧半胱氨酸（3- 100 μ M）等未表现出任何可检测的药理作用的化合物具有降低脊髓反射单突触成分振幅的活性，表现为“L-F_2 CCG-I启动”。除使君子酸启动外，L-F_2CCG-I启动也可能与神经可塑性有关。L-F_2CCG-I、DL-α-氨基庚二酸和羧半胱氨酸为阐明神经可塑性机制提供了有用的药理学探针。少

On the basis of the idea that there are positive relationships among the metabotropic glutamate receptors, quisqualate priming and neural plasticity, the priming induced by some agonists for metabotropic glutamate receptors was examined.It was found that AMPB [L-2-amino-4- (methylphosphino) butyric acid] is related to the quisqualate priming, and L-F2CCG-I [2S,1'S,2'S) -2- (2-carboxy-3,3-difluorocycloproyl) glycine] was the most potent on a molar basis in causing depolarization among 8 stereoisomers of 2- (2-carboxy-3,3-difluorocyclopropyl) glycine, the threshold concentration being about 1muM.The depolarization evoked by L-F_2-CCG-I (10-30muM) was effectively depressed by MCPG (1mM), and was only slightly decreased by high concentrations of D-AP5 (100muM), but not by CNQX (100muM), suggesting that L-F_2CCG-I activated metabotropic glutamate receptors. L-F_2CCG-I preferentially depressed the monosynaptic component of the spinal reflex about 3 times as much as more effectively than (2S, … More 1'S,2'S) -2- (carboxy-cyclopropyl) glycine (L-CCG-I). The inhibitory action of L-F_2CCG-I (0.2muM-0.7muM) on monosynaptic excitation was effectively blocked by MCCG (0.3 mM-1mM) and MAP4 (0.3mM). DL-alpha-Aminopimelic acid, at concentrations lower than 0.1mM (the threshold concentration : 3muM), selectively potentiated the inhibition of monosynaptic excitation caused by L-CCG-I,L-F_2CCG-I and (2S,1'S,2'R,3'S) -2- (2-carboxy-3-methoxymethylcyclopropyl) glycine (trans-MCG-I), but the action of (2S,1'R,2'R,3'R) -2- (2,3-dicarboxycyclopropyl) glycine (DCG-IV), L-AP4, (1S,3R) -ACPD and baclofen was not affected at all by DL-alpha-aminopimelic acid.Once L-F_2CCG-I was applied to the spinal cord preparation of newborn rats, very low concentrations of L-glutamate (for example, 30muM), DL-alpha-aminopimelic acid and carbocysteine (3-100muM), which did not show any detectable pharmacological actions, got an activity to decrease the amplitude of the monosynaptic component of spinal reflexes, showing the 'L-F_2CCG-I priming'. In addition to the quisqualate priming, L-F_2CCG-I priming is also conceivable to be related to the neural plasticity. L-F_2CCG-I,DL-alpha-aminopimelic acid and carbocysteine would provide useful pharmacological probes for elucidating the mechanisms for neural plasticity. Less