| Research Abstract |
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
|
