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Keywords:

  • glycine antagonist site;
  • AIDS;
  • N-methyl-d-aspartate;
  • glutamate neurotoxicity;
  • mammalian central neurons;
  • retinal ganglion cells

Abstract

Prior studies with in vitro model systems have suggested that at least part of the neurological manifestations of AIDS may stem from neuronal injury involving the HIV-1 coat protein gp120. This form of neuronal damage is most probably mediated indirectly by a complex set of cellular interactions among macrophages, astrocytes, and neurons, resulting in a final common pathway of overstimulation of N-methyl-d-aspartate (NMDA) receptors. We studied the neuroprotective effect from gp120-induced neuronal injury of an antagonist of the glycine site of the NMDA receptor, 7-chlorokynurenate. In identified rat retinal ganglion cells in culture, we found that 50 μM 7-chlorokynurenate significantly abrogated the injury engendered by 20 pM gp120. Addition of 300 μM exogenous glycine prevented this protective effect of 50 μM 7-chlorokynurenate. These data suggest that glycine site antagonists of the NMDA receptor may have therapeutic potential for ameliorating neuronal damage associated with gp120.