Two different families of NMDA receptors in mammalian brain: physiological function and role in neuronal development and degeneration.
The data from purification, ligand binding, reconstitution and immunochemical studies indicate that there is a group of small molecular size proteins (30 to 70 kDa) that form what appear to be NMDA receptor complexes. Based on cell biological studies of the expression and localization of one of the subunits of this complex, the glutamate-binding subunit, it appears that this putative NMDA receptor plays a key role in neuronal sensitivity to NMDA and in neuronal survival in early development. However, brain neurons quite clearly express another family of proteins which have all functional characteristics of an NMDA receptor plus a great degree of variability that can account for the varieties of NMDA receptors found in brain. This family of NMDA receptors, the NMDAR1 and NMDAR2, are not homologous to the small molecular size proteins of the previously described receptor complex that was isolated from synaptic membranes. If brain neurons are indeed expressing two very diverse families of proteins that function as glutamate/NMDA receptors, this must be an indication that either there is a very selective expression of one of these forms in specific neurons or neuronal compartments, or that one of these forms of the receptor plays an important role in unique functions of the cell, such as synaptic plasticity or neurodegeneration. As more information is gathered about the structure and function of these receptors, a better understanding of the expression and role of these families of receptor proteins in normal neuronal excitability will be achieved. This enhanced level of understanding about the function and activity of these receptors will be needed in order to identify more precisely the NMDA receptors most affected in pathological conditions such as hyperammonemia.
Michaelis
E K
EK
Department of Pharmacology and Toxicology, University of Kansas, Lawrence 66045.
D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D003001:Cloning, Molecular; D016202:N-Methylaspartate / Q000494:pharmacology; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate