2,4,5-TRIHYDROXYPHENYLALANINE (6-HYDROXY-DOPA) DISPLACES [H-3] AMPA BINDING IN RAT STRIATUM

NEUROSCIENCE LETTERS

卷:132

Article

CHA, JHJ ; DURE, LS ; SAKURAI, SY ; PENNEY, JB ; YOUNG, AB

关键词: AUTORADIOGRAPHY;    EXCITATORY AMINO ACID;    L-DOPA;    NEUROTOXICITY;    STRIATUM;   

DOI  :  10.1016/0304-3940(91)90432-S

来源: Elsevier

【 摘 要 】

Excitatory amino acid (EAA) receptor-mediated events have recently been implicated in dopaminergic mechanisms of neurotoxicity. 2,4,5-Trihydroxyphenylalanine (6-hydroxy-DOPA, TOPA), the ortho-hydroxylated derivative of the dopamine precursor 2,4-dihydroxyphenylalanine (L-DOPA), has recently been reported to have neurotoxic properties which are blocked by CNQX, a specific antagonist of the AMPA class of non-N-methyl-D-aspartate (non-NMDA) EAA receptors. We report here that 6-hydroxy-DOPA is a selective displacer of [H-3]AMPA binding in rodent brain. 6-Hydroxy-DOPA was as potent as kainate in displacing [H-3]AMPA binding, with an IC50 value of 32-mu-M. Ineffective displacers of [H-3]AMPA binding included dopamine, 6-hydroxydopamine, L-DOPA, D-DOPA, carbidopa, DOPAC, beta-methylamino-L-alanine, 2,4-dihydroxyphenylacetyl-L-asparagine, homogentisic acid, 2,4-dihydroxyphenylacetic acid, amantadine, and threo-DOPS. 6-Hydroxy-DOPA (100-mu-M) also displaced 20% of [H-3]kainate binding, but did not displace binding to NMDA, phencyclidine (PCP), or dopaminergic (D1 and D2) receptors. These data raise the possibility that 6-hydroxy-DOPA or another abnormal metabolite of L-DOPA could act as an excitotoxic agent via action at AMPA receptors. Given that non-NMDA receptors are postulated to play a role in neurotoxic events, these data provide an additional mechanism via which EAA receptor-mediated events could produce neurodegeneration in areas of brain with dopaminergic innervation.

【 授权许可】

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