Article date: 1992/11/1
PubMed ID: 1281890
Journal name: Journal of neuroscience research (ISSN: 0360-4012)
Pharmacological characterization of the action of the novel non-N-methyl-D-aspartate (non-NMDA) antagonist AMOA (2-amino-3-[3-(carboxymethoxy)-5-methylisoxazol-4-yl]propionate) on glutamate receptors was investigated in Xenopus oocytes injected with mouse brain mRNA. AMOA (150 microM) produced a nearly parallel shift to the right of the dose-response curve for kainate-induced currents. AMOA was found to have two different effects on AMPA receptors: 1) currents elicited by low concentrations of AMPA (6 microM) were inhibited by AMOA with an IC50 value of 160 +/- 19 microM and 2) currents elicited by high concentrations of AMPA (100 microM) were potentiated with an IC50 value of 88 +/- 22 microM. The maximal potentiating effect of AMOA on AMPA currents was around 170%. Furthermore, the two opposing effects of AMOA on AMPA responses are specific for the L-configuration of AMOA. This unusual antagonistic/agonistic property of AMOA may explain its unusual properties with regard to antagonism of non-NMDA receptor-mediated events previously described.
Author List: Wahl P, Nielsen B, Krogsgaard-Larsen P, Hansen J J, Schousboe A, Miledi R
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: Isoxazoles; Propionates; RNA, Messenger; Receptors, Amino Acid; 2-amino-3-(3-(carboxymethoxy)-5-methylisoxazol-4-yl)propionic acid; Ibotenic Acid; N-Methylaspartate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Kainic Acid;
Mesh terms: Animals; Brain Chemistry/physiology; Dose-Response Relationship, Drug; Female; Ibotenic Acid/analogs & derivatives; Isoxazoles/pharmacology; Kainic Acid/pharmacology; Membrane Potentials/drug effects; Mice; N-Methylaspartate/antagonists & inhibitors; Oocytes/metabolism; Propionates/pharmacology; RNA, Messenger/metabolism; Receptors, Amino Acid/antagonists & inhibitors; Stereoisomerism; Xenopus laevis; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;