Basic research on metabotropic glutamate receptors and neural plasticity.

基于亲代谢性谷氨酸受体、准定量启动与神经可塑性之间存在正相关关系的观点，考察了几种激动剂对代谢性谷氨酸受体的启动作用。发现AmpB[L-2-氨基-4-(甲基膦)丁酸]与准启动有关，而L-F2CCG-I[2S，1‘S，2’S]-2-(2-羧基-3，3-二氟环丙基)甘氨酸是引起2-(2-羧基-3，3-二氟环丙基)甘氨酸8个立体异构体去极化的最强的MCPG(1 MM)可有效抑制L-F_2-CCG-I(10-30µM)引起的去极化，高浓度D-AP_5(100µM)仅有轻微的抑制作用，而CNQX(100µM)则不能。提示L-F_2-CCG-I激活了代谢型谷氨酸受体。L-F_2CCG-I对脊髓反射单突触成分的抑制作用约为(2S，…)的3倍更多的1‘S，2’S)-2-(羧基环丙基)甘氨酸(L-CCG-I)。MCCG(0.3 mM-1 mM)和MAP4(0.3 mM)能有效阻断MCCG-I(0.2-0.7 mM)对单突触兴奋的抑制作用。当浓度低于0.1 mM(阈值浓度：3µM)时，DL-α-氨基甲酸选择性地增强L-CCG-I、L-F_2CCG-I和(2S，1‘S，2’R，3‘S)-2-(2-羧基-3-甲氧甲基环丙基)甘氨酸(反式-MCG-I)对单突触兴奋的抑制作用，而(2S，1’R，2‘R，3’R)-2-(2，3-二羧基环丙基)甘氨酸(DCG-IV)，(1S，L，AP4，(1S，AP4)，(1S，2‘R，3’R)-2-(2，3-二羧基环丙基)甘氨酸(2S，1‘R，2’R，3‘R)-2-(2，3-二羧基环丙基)甘氨酸(DCG-IV)，(1S，L-AP4，(1S，2’R，3‘R)-2-(2，3-二羧环丙基)甘氨酸L-F_2CCG-I用于新生大鼠脊髓制备后，极低浓度的L-谷氨酸(如30µM)、DL-α-氨基戊二酸和氨基半胱氨酸(3-100µM)对脊髓反射单突触成分的幅度无明显影响，表现为“L-F_2CCG-I引发”。除准启动外，L-F_2CCG-I启动也可能与神经可塑性有关。L-F_2CCG-I、DL-α-氨基己酸和半胱氨酸为阐明神经可塑性的机制提供了有用的药理探针。较少

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