2887240

Characterization of quisqualate-type L-glutamate receptors in the retina.

Article date: 1987/6/23

PubMed ID: 2887240

Journal name: Brain research (ISSN: 0006-8993)

ABSTRACT

In the vertebrate retina excitatory transmission seems to be mediated mainly by excitatory amino acids; glutamate and/or aspartate are the most viable candidates to subserve this function. Postsynaptic receptors for N-methyl-D-aspartate (NMDA), kainate (KA), quisqualate (QA) and 2-amino-4-phosphonobutyric acid have been electrophysiologically identified. In this work we have tried to identify and characterize QA receptors through the binding of the most specific analogue available for this receptor: [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA). AMPA binding to retinal membranes was sodium- and temperature-independent, with optimum pH at 6-7. Ligand-receptor interaction was reversible and saturable. Pharmacologically, glutamate analogues were more active displacers than NMDA analogues: AMPA greater than (RS)-3-hydroxy-4,5,6,7-tetrahydro-isoxazolo-(5,4-C)-pyridine-7-car boxylic acid = L-Glu = QA; with IC50 in the low microM range. Glutamic acid diethylester was uneffective while KA and cis-2,3-piperidine dicarboxylate were potent inhibitors of binding. Binding was stereospecific, L-isomers being more effective displacers than D-forms. Subcellular distribution showed binding concentrated in the inner plexiform layer (IPL), but also present in the outer plexiform layer (OPL). Kinetics of [3H]AMPA binding showed a high affinity kB = 1-2 microM in membranes from complete retina, IPL and OPL, with binding sites concentrated in P2 (Bmax = 16.2 pmol/mg protein). Our results provide biochemical evidence for the presence and distribution of physiologically relevant QA receptors in the chick retina which is in agreement with previous physiological findings.

Author List: López-Colomé A M, Somohano F

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Glutamates; Receptors, AMPA; Receptors, Drug; Receptors, Glutamate; Receptors, Neurotransmitter; Ibotenic Acid; Aspartic Acid; Glutamic Acid; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

Mesh terms: Animals; Animals, Newborn; Aspartic Acid/metabolism; Binding, Competitive; Chickens; Glutamates/metabolism; Glutamic Acid; Hydrogen-Ion Concentration; Ibotenic Acid/analogs & derivatives; Kinetics; Receptors, AMPA; Receptors, Drug/analysis; Receptors, Glutamate; Receptors, Neurotransmitter/analysis; Retina/analysis; Subcellular Fractions/metabolism; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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