NDLI: Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine.

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Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine.

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Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Watkins, J. C. Olverman, H. J. Nguyen, L. Monaghan, D. T. Cotman, C. W.
Description	Author Affiliation: Monaghan DT ( Division of Neurosurgery, University of California, Irvine 92717.);
Abstract	The N-methyl-D-aspartate (NMDA) receptor, a subtype of excitatory amino acid receptor, mediates synaptic responses in many regions of the central nervous system. This receptor plays a critical role in the mechanisms of both synaptic plasticity and excitotoxicity. Although these receptors were generally thought to be a single homogeneous receptor population, we report observations indicating that two anatomically distinct forms of the NMDA-receptor complex exist. (i) The distribution of NMDA receptors, as labeled by the NMDA agonist L-[3H]glutamate, differs from that obtained with the radiolabeled antagonist 3H-labeled 3-[(+/-)2-carboxypiperazine-4-yl]propyl-1-phosphonic acid [( 3H]CPP). Relative to L-[3H]glutamate, [3H]CPP binding is low in the striatum and septum and high in the thalamus and inner cerebral cortex. (ii) NMDA antagonists are relatively more potent than agonists at displacing L-[3H]glutamate binding in the thalamus and cerebral cortex; agonists are relatively more potent in the striatum and cerebellum. (iii) Glycine, which potentiates NMDA-receptor responses to glutamate, causes a greater percentage increase in L-[3H]glutamate binding to NMDA receptors in the thalamus and cerebral cortex than in the striatum, septum, and cerebellum. Radiolabeled NMDA-antagonist binding, in contrast, is inhibited by glycine. Thus, as observed for gamma-aminobutyric acid type A receptors, NMDA receptors have an agonist-preferring binding-site population and an antagonist-preferring binding site population. These may represent two distinct receptors and/or two interconverting forms. It could be of significant clinical importance if these two sites differ in their response to NMDA.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	24
Volume Number	85
Language	English
Publisher	National Academy of Sciences
Publisher Date	1988-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Aspartic Acid Analogs & Derivatives Glycine Pharmacology Receptors, Neurotransmitter Pharmacokinetics Animals Metabolism Autoradiography Binding Sites Brain Glutamates Glutamic Acid N-Methylaspartate Piperazines Rats, Inbred Strains Receptors, N-Methyl-D-Aspartate Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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