Effect of the L- or D-aspartate on ecto-5'nucleotidase activity and on cellular viability in cultured neurons: participation of the adenosine A(2A) receptors.
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 A(2A) receptors (ZM 241385) prevented totally the L- Asp-induced cellular death, but partially the neurotoxicity induced by D-Asp and the antagonist of adenosine A(1) 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 A(2A) receptor which is probably co-operating with the neurotoxicity induced by amino acids.
Boeck
C R
CR
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Kroth
E H
EH
Bronzatto
M J
MJ
Vendite
D
D
D015720:5'-Nucleotidase / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D026603:D-Aspartic Acid / Q000737:chemistry / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000378:metabolism*
D043705:Receptor, Adenosine A2A; D001224:Aspartic Acid; D018698:Glutamic Acid; D000249:Adenosine Monophosphate; D026603:D-Aspartic Acid; D016202:N-Methylaspartate; D015720:5'-Nucleotidase