title: Induction of glutamate binding sites in hippocampal membranes by transient exposure to high concentrations of glutamate or glutamate analogs.
abstract: The number of Na+-independent, Cl--dependent glutamate binding sites in rat hippocampal membranes is increased two- to fourfold after pre-exposing isolated membranes or hippocampal slices to high concentrations (0.1-10 mM) of L-glutamate or of glutamate analogs with high affinity for this binding site, such as quisqualate, homocysteate, or aminoadipate. N-Methylaspartate and kainate are ineffective. A similar binding increase is induced by transient exposure to the dipeptide tyrosylglutamate. The newly induced binding sites appear to be identical with pre-existing Cl--dependent binding sites by several criteria: They have a similar pharmacological profile, they are sensitive to low concentrations of Na+, and the number of sites can be further increased by transient exposure to micromolar calcium concentrations. Moreover, binding of [3H]APB, a ligand selective for the Cl--dependent glutamate binding sites, is also increased after glutamate preincubation. The induction of binding sites by high glutamate concentrations, described herein, is calcium-independent, not inhibited by leupeptin and, therefore, different from the previously described activation of binding sites by a calcium-sensitive protease. The high concentration of ligand needed to induce increased binding suggests the presence in hippocampal membranes of a binding site with low, millimolar affinity that is functionally related to the known high-affinity binding sites. Several interpretations of the observed effects and their implications for the possible relationship between the binding site and the synaptic receptor are discussed.
authors.forename: M
authors.initials: M
authors.lastname: Kessler
authors.forename: M
authors.initials: M
authors.lastname: Baudry
authors.forename: J T
authors.initials: JT
authors.lastname: Cummins
authors.forename: S
authors.initials: S
authors.lastname: Way
authors.forename: G
authors.initials: G
authors.lastname: Lynch
mesh_terms: D015763:2-Amino-5-phosphonovalerate; D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001665:Binding Sites; D002712:Chlorides / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis* / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000613:Aminobutyrates; D002712:Chlorides; D005971:Glutamates; D010069:Oxadiazoles; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D012503:Saponins; D006710:Homocysteine; C007956:homocysteic acid; D015074:2-Aminoadipic Acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D012964:Sodium; C012729:2-amino-4-phosphonobutyric acid; D014633:Valine; D007608:Kainic Acid