[Modulation of NMDA-receptor efficiency by intracellular agents]

Glutamate in one of the principle transmitters in the CNS. Ionotropic receptors of glutamate selectively activated by N-methyl-d-aspartate (NMDA) play an important role in the processes of development, learning, memory etc. Hyperactivation of these receptors is responsible for a number of pathological processes. Due to their importance, the NMDA receptors are subjected to strong modulatory influences of different modulatory systems of the brain. Modulation of the NMDA receptor efficiency by extracellular factors is well known and described in a number of reviews, while their modulation by intracellular factors is less known and has not yet been reviewed. This review presents the experimental data concerning a modulatory control of the NMDA receptors by intracellular factors. Some of these factors are: phosphorylation by protein kinases (PK) C, A, Ca2+/calmodulin-dependent PK II, tyrosine kinases; dephosphorylation by protein phosphatases 1, 2A, 2B; interaction with regulatory peptides and cytoskeleton; influence of surrounding lipids etc. Interaction between these factors creates a labile intracellular system, which efficiently modulates activity of the NMDA receptors mediating the activity of different extracellular active compounds (neurotransmitters, neurotoxins, drugs etc.). A cheme summarizing different intracellular pathways of modulation of the NMDA receptor efficiency is described.