| Autor: |
Glushakov, A.V., Dennis, D.M., Morey, T.E., Sumners, C., Cucchiara, R.F., Seubert, C.N., Martynyuk, A.E. |
| Předmět: |
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| Zdroj: |
Molecular Psychiatry; 2002, Vol. 7 Issue 4, p359, 9p |
| Abstrakt: |
Hippocampal N-methyl-D-aspartate receptors (NMDARs) are thought to be involved in the regulation of memory formation and learning. Investigation of NMDAR function during experimental conditions known to be associated with impaired cognition in vivo may provide new insights into the role of NMDARs in learning and memory. Specifically, the mechanism whereby high concentrations of L-phenylalanine (L-Phe) during phenylketonuria (>1.2 mM) cause mental retardation remains unknown. Therefore, the effects of L-Phe on NMDA-activated currents (I[sub NMDA]) were studied in cultured hippocampal neurons from newborn rats using the patch-clamp technique. L-Phe specifically and reversibly attenuated I[sub NMDA] in a concentration-dependent manner (IC[sub 50] = 1.71 ± 0.24 mM). In contrast, L-tyrosine (L-Tyr), an amino acid synthesized from L-Phe in normal subjects, did not significantly change I[sub NMDA]. Although the L-Phe-I[sub NMDA] concentration-response relationship was independent of the concentration of NMDA, it was shifted rightward by increasing the concentration of glycine. Consistent with an effect of L-Phe on the NMDAR glycine-binding site, L-Phe (1 mM) did not attenuate I[sub NMDA] in the presence of D-alanine (10 µM). Furthermore, L-Phe significantly attenuated neither glutamate-activated current in the presence of MK-801, nor current activated by AMPA. The finding that L-Phe inhibits specifically NMDAR current in hippocampal neurons by competing for the glycine-binding site suggests a role for impaired NMDAR function in the development of mental retardation during phenylketonuria and accordingly an important role for NMDARs in memory formation and learning. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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