1281252

Agonist- and subunit-dependent potentiation of glutamate receptors by a nootropic drug aniracetam.

Article date: 1992/11/1

PubMed ID: 1281252

Journal name: Brain research. Molecular brain research (ISSN: 0169-328X)

ABSTRACT

GluR1 and GluR2 cDNAs encoding non-NMDA subtypes of glutamate receptor were isolated from a rat brain cDNA library by Boulter et al. (Science, 249 (1990) 1033-1037). Functional receptors activated by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and glutamate were expressed in Xenopus oocytes injected with GluR1, GluR2 or a mixture of GluR1 and GluR2 RNAs. In GluR1-expressed oocytes, 1 mM aniracetam potentiated AMPA-induced currents by 99 +/- 10% (mean +/- S.E.M., n = 5) and glutamate-induced currents by 140 +/- 8% (n = 4), but little affected kainate-induced currents. Aniracetam was effective from a concentration of 0.1 mM, and it exhibited more conspicuous effects with the increase of the dose. In oocytes injected with GluR1 plus GluR2 RNAs, aniracetam more markedly potentiated current responses to AMPA and glutamate than those in oocytes injected with GluR1 RNA alone. For example, 1 mM aniracetam potentiated AMPA-induced currents by 396 +/- 76% (n = 4) and glutamate-induced currents by 970 +/- 65% (n = 5) in oocytes injected with 10% GluR1 and 90% GluR2 RNAs. In these oocytes, however, the potentiation of kainate-induced currents by 1 mM aniracetam was only 8 +/- 5% (n = 4). Thus, we conclude that the potentiation of the AMPA/kainate receptor by aniracetam depends on both species of agonists and subunit composition of the receptor.

Author List: Tsuzuki K, Takeuchi T, Ozawa S

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

Substances mentioned in the article: Glutamates; Psychotropic Drugs; Pyrrolidinones; Receptors, Glutamate; Ibotenic Acid; Glutamic Acid; aniracetam; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Kainic Acid;

Mesh terms: Animals; Drug Synergism; Evoked Potentials/drug effects; Glutamates/pharmacology; Glutamic Acid; Ibotenic Acid/analogs & derivatives; Kainic Acid/pharmacology; Membrane Potentials/drug effects; Oocytes/drug effects; Psychotropic Drugs/pharmacology; Pyrrolidinones/pharmacology; Rats; Receptors, Glutamate/drug effects; Xenopus laevis; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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