Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus oocytes
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Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus oocytes. / Wahl, P; Nielsen, B; Krogsgaard-Larsen, P; Hansen, Jan J.; Schousboe, A; Miledi, R.
In: Journal of Neuroscience Research, Vol. 33, No. 3, 11.1992, p. 392-7.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 33
SP - 392
EP - 397
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 3
ER -
ID: 171785719