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Title: Evidence for heterogenous glycine domains but conserved multiple states of the excitatory amino acid recognition site of the NMDA receptor: regional binding studies with [3H]glycine and [3H]L-glutamate.
Austin Authors: O'Shea, R D;Manallack, D T;Conway, Elizabeth L;Mercer, L D;Beart, P M
Affiliation: University of Melbourne, Clinical Pharmacology and Therapeutics, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 16-May-1991
Publication information: Experimental Brain Research; 86(3): 652-62
Abstract: The possible heterogeneity of the agonist and glycine sites of the N-methyl-D-aspartate (NMDA) receptor-complex was examined using receptor binding techniques. Binding of [3H]L-glutamate [( 3H]GLU) and [3H]glycine to synaptic membranes of cerebral and cerebellar cortices, and membranes of a granule cell preparation of rat cerebellum, was characterized. [3H]Glycine always labelled a single population of sites; densities of binding sites (Bmax) in cortical, cerebellar and "granule" membranes were 3.1, 0.87 and 3.6 pmol/mg protein, respectively. Dissociation constants (Kd) in the same three preparations were 0.13, 0.31 and 1.9 microM, respectively. In competition studies, D-cycloserine, but not D-serine and 7-chlorokynurenate, showed varying potency between the membrane preparations, and analysis of variance (ANOVA) revealed a significant interaction between ligands and membrane fractions. Binding of [3H]GLU was saturable and to a single population of sites: Kd 0.5-0.9 microM and Bmax 3.2-3.6 pmol/mg protein. In all three membrane preparations the rank order of potency of NMDA agonists as inhibitors of the binding of [3H]GLU was always L-aspartate greater than L-cysteate greater than L-cysteinesulphinate greater than L-serine-O-sulphate greater than ibotenate greater than L-homocysteate. NMDA, quinolinate and competitive NMDA antagonists were only weak inhibitors of the binding of [3H]GLU and never fully inhibited specific binding. Other subtype-selective excitatory amino acids were very weak or ineffective inhibitors of binding. Binding of NMDA agonists was better described by a two site model whereby the proportion of high affinity sites did not vary significantly across the three membrane preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
Gov't Doc #: 1684753
Journal: Experimental Brain Research
Type: Journal Article
Subjects: Animals
Binding, Competitive.drug effects
Cerebellar Cortex.anatomy & histology.metabolism
Cerebral Cortex.anatomy & histology.metabolism
Glutamic Acid
In Vitro Techniques
Kynurenic Acid.analogs & derivatives.pharmacology
Rats, Inbred Strains
Receptors, Amino Acid
Receptors, Cell Surface.metabolism
Receptors, N-Methyl-D-Aspartate.antagonists & inhibitors.metabolism
Appears in Collections:Journal articles

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