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.
journal_name
J Neurosci Resjournal_title
Journal of neuroscience researchauthors
Wahl P,Nielsen B,Krogsgaard-Larsen P,Hansen JJ,Schousboe A,Miledi Rdoi
10.1002/jnr.490330305keywords:
subject
Has Abstractpub_date
1992-11-01 00:00:00pages
392-7issue
3eissn
0360-4012issn
1097-4547journal_volume
33pub_type
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