Molecular biological studies on nuclear transcription factors expressed through the N-methyl-D-aspartate receptor complex.

DNA binding activities of several transcription factors were evaluated in nuclear extracts from brains of mice which were intracerebroventricularly injected with N-methyl-D-aspartic acid (NMDA) using gel retardation electrophoresis. An injection of NMDA increased binding of both probes for activator protein 1 (AP1) and cyclic AMP response element binding protein (CREB) 1 to 5 h after the injection compared with that of saline, in a dose-dependent manner at doses from 0.05 to 0.4 micrograms. However, no significant alterations were found in binding of probes for other 4 different transcription factors tested following the injection of NMDA up to 4 h after the administration. These included promoter-specific transcription factor, nuclear factor kappa B, activator protein 2 and octamer binding protein. Potentiation of the AP1 and CREB binding was prevented in a dose-dependent manner by the administration of either of the noncompetitive NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine, the NMDA antagonist D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid, the glycine antagonist 5,7-dichlorokynurenic acid, or the proposed polyamine antagonist ifenprodil. In contrast, the AP1 binding was not consistently affected up to 4 h following intracerebroventricular injections of other agonists including DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic, kainic, and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acids, in contrast to the severity of convulsive seizures by the former 2 excitants. These results support the proposal that an intracerebroventricular injection of NMDA may selectively potentiate DNA binding activities of both AP1 and CREB through in vivo activation of the NMDA receptor complex in the murine brain.