1648177

Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA.

Article date: 1991/6/27

PubMed ID: 1648177

Journal name: Nature (ISSN: 0028-0836)

ABSTRACT

Fast excitatory transmission in the vertebrate central nervous system is mediated mainly by L-glutamate. On the basis of pharmacological, physiological and agonist binding properties, the ionotropic glutamate receptors are classified into NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate) and kainate subtypes. Sequence homology between complementary DNA clones encoding non-NMDA glutamate receptor subunits reveals at least two subunit classes: the GluR1 to GluR4 class and the GluR5 class. Here we report the cloning and expression of a functional rat glutamate receptor subunit cDNA, GluR6, which has a very different pharmacology from that of the GluR1-GluR4 class. Receptors generated from the GluR1-GluR4 class have a higher apparent affinity for AMPA than for kainate. When expressed in Xenopus oocytes the homomeric GluR6 receptor is activated by kainate, quisqualate and L-glutamate but not by AMPA, and the apparent affinity for kainate is higher than for receptors from the GluR1-GluR4 class. Desensitization of the receptor was observed with continuous application of agonist. The homomeric GluR6 glutamate receptor exhibits an outwardly rectifying current-voltage relationship. In situ hybridizations reveal a pattern of GluR6 gene expression reminiscent of the binding pattern obtained with [3H]kainate.

Author List: Egebjerg J, Bettler B, Hermans-Borgmeyer I, Heinemann S

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

Substances mentioned in the article: Receptors, Glutamate; Receptors, Neurotransmitter; Ibotenic Acid; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; DNA; Kainic Acid;

Mesh terms: Amino Acid Sequence; Animals; Brain Chemistry; Cerebellum/chemistry; Cloning, Molecular; DNA/genetics; Ibotenic Acid/analogs & derivatives; Kainic Acid/metabolism; Mice; Molecular Sequence Data; Nucleic Acid Hybridization; Oocytes/metabolism; Rats; Receptors, Glutamate; Receptors, Neurotransmitter/analysis; Tissue Distribution; Transfection; Xenopus; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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