Modulation of NMDA receptor responsiveness by neurotransmitters, drugs and chemical modification.
The NMDA receptor is intimately involved an a wide range of pathophysiological processes in the mammalian brain, including epilepsy and ischemia-induced neurodegeneration. The widespread distribution of NMDA receptors places almost every area of the brain at risk from NMDA receptor over-activity. However, it is clear that the central nervous system can function effectively without imminent danger of self-destruction. The focus of this review is the processes that control NMDA receptor responsiveness in vivo. The review will cover the modulation of the receptor by Mg2+, glycine, Zn2+ and polyamines that is believed to occur by virtue of interaction with distinct ligand binding sites on the NMDA receptor complex. Studies suggesting a role for receptor phosphorylation and for redox modulation will be discussed. Finally, some evidence for indirect regulation of cellular responses to NMDA receptor activation by other neurotransmitters will be presented.
Reynolds
I J
IJ
Department of Pharmacology, University of Pittsburgh, PA 15261.
D000818:Animals; D005998:Glycine / Q000494:pharmacology; D008024:Ligands; D008274:Magnesium / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D011073:Polyamines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology
D008024:Ligands; D018377:Neurotransmitter Agents; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; D008274:Magnesium; D015032:Zinc; D005998:Glycine