Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus Oocytes

✍ Scribed by P. Wahl; B. Nielsen; P. Krogsgaard-Larsen; J. J. Hansen; Professor A. Schousboe; R. Miledi

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 506 KB
• Volume: 33
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490330305

✦ Synopsis

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 ooccytes injected with mouse brain mRNA. AMOA (150 μM) 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 μM) were inhibited by AMOA with an IC~50~ value of 160 ± 19 μM and (2) currents elicited by high concentrations of AMPA (100 μM) were potentiated with an IC~50~ value of 88 ± 22 μM. 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.