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

TY - JOUR

T1 - Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus oocytes

AU - Wahl, P

AU - Nielsen, B

AU - Krogsgaard-Larsen, P

AU - Hansen, Jan J.

AU - Schousboe, A

AU - Miledi, R

PY - 1992/11

Y1 - 1992/11

N2 - 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.

AB - 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.

KW - Animals

KW - Brain Chemistry

KW - Dose-Response Relationship, Drug

KW - Female

KW - Ibotenic Acid

KW - Isoxazoles

KW - Kainic Acid

KW - Membrane Potentials

KW - Mice

KW - N-Methylaspartate

KW - Oocytes

KW - Propionates

KW - RNA, Messenger

KW - Receptors, Amino Acid

KW - Stereoisomerism

KW - Xenopus laevis

KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1002/jnr.490330305

DO - 10.1002/jnr.490330305

M3 - Journal article

C2 - 1281890

SN - 0360-4012

VL - 33

SP - 392

EP - 397

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

IS - 3

ER -