Abstract
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.
| Original language | English |
|---|---|
| Journal | Journal of Neuroscience Research |
| Volume | 33 |
| Issue number | 3 |
| Pages (from-to) | 392-7 |
| Number of pages | 6 |
| ISSN | 0360-4012 |
| DOIs | |
| Publication status | Published - Nov 1992 |
Keywords
- Animals
- Brain Chemistry
- Dose-Response Relationship, Drug
- Female
- Ibotenic Acid
- Isoxazoles
- Kainic Acid
- Membrane Potentials
- Mice
- N-Methylaspartate
- Oocytes
- Propionates
- RNA, Messenger
- Receptors, Amino Acid
- Stereoisomerism
- Xenopus laevis
- alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.