2,4,5-Trihydroxyphenylalanine (6-hydroxy-DOPA) displaces [3H]AMPA binding in rat striatum

Academic Article

Abstract

  • 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 [3H]AMPA binding in rodent brain. 6-Hydroxy-DOPA was as potent as kainate in displacing [3H]AMPA binding, with an IC50 value of 32 μM. Ineffective displacers of [3H]AMPA binding included dopamine, 6-hydroxydopamine, l-DOPA, d-DOPA, carbidopa, DOPAC, β-methylamino-l-alanine, 2,4-dihydroxyphenylacetyl-l-asparagine, homogentisic acid, 2,4-dihydroxyphenylacetic acid, amantadine, and threo-DOPS. 6-Hydroxy-DOPA (100 μM) also displaced 20% of [3H]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. © 1991.
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    Author List

  • Cha JHJ; Dure LS; Sakurai SY; Penney JB; Young AB
  • Start Page

  • 55
  • End Page

  • 58
  • Volume

  • 132
  • Issue

  • 1