Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus oocytes.
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.
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009865:Oocytes / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017459:Receptors, Amino Acid / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D007555:Isoxazoles; D011422:Propionates; D012333:RNA, Messenger; D017459:Receptors, Amino Acid; C066116:2-amino-3-(3-(carboxymethoxy)-5-methylisoxazol-4-yl)propionic acid; D007051:Ibotenic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid