Effect of the L- or D-aspartate on ecto-5'nucleotidase activity and on cellular viability in cultured neurons: participation of the adenosine A₂A receptors
2007
Boeck, C. R | Kroth, E. H | Bronzatto, M. J | Vendite, D
Glutamate increases the extracellular adenosine levels, an important endogenous neuromodulator. The neurotoxicity induced by glutamate increases the ecto-5'-nucleotidase activity in neurons, which produces adenosine from AMP. L- and D-aspartate (Asp) mimic most of the actions of glutamate in the N-methyl-D-aspartate (NMDA) receptors. In the present study, both amino acids stimulated the ecto-5'-nucleotidase activity in cerebellar granule cells. MK-801 and AP-5 prevented the L- and D-Asp-evoked activation of ecto-5'-nucleotidase. Both NMDA receptor antagonists prevented completely the damage induced by L-Asp, but partially the D-Asp-induced damage. The antagonist of adenosine A₂A receptors (ZM 241385) prevented totally the L- Asp-induced cellular death, but partially the neurotoxicity induced by D-Asp and the antagonist of adenosine A₁ receptors (CPT) had no effect. The results indicated a different involvement of NMDA receptors on the L- or D-Asp-evoked activation of ecto-5'-nucleotidase and on cellular damage. The adenosine formed from ecto-5'-nucleotidase stimulation preferentially acted on adenosine A₂A receptor which is probably co-operating with the neurotoxicity induced by amino acids.
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