Reactive oxygen production by glutamate agonists in dissociated cerebellar cells: a flow cytometric study.
1. The effect of glutamate, N-methyl-D-aspartate (NMDA) and kainate on radical oxygen species (ROS) production and calcium influx was studied in dissociated cerebellar granule cells with the use of flow cytometry. 2. Glutamate and NMDA induced an intracellular ROS increase by an activation of NMDA receptors. 3. (+)MK-801 inhibited the effect on ROS production of both agonists (IC50 values of 1.52 +/- 0.05 and 0.71 +/- 0.02 microM, respectively). 4. (+)MK-801 inhibited the intracellular calcium increase induced by glutamate and NMDA, whereas 6-cyano-7-nitroquinoxaline-2,3-dione inhibited that induced by kainate. 5. NG-Nitro-L-arginine, but not nitrendipine, inhibited the ROS production induced by glutamate agonists. Consequently, nitric oxide synthase might play an important role in the neurotoxic process induced by excitatory amino acids.
Sureda
F X
FX
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari Pedralbes, Spain.
Camins
A
A
Pallàs
M
M
Trullàs
R
R
Escubedo
E
E
Camarasa
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002525:Cerebellar Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005434:Flow Cytometry / Q000379:methods*; D009568:Nitrendipine / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D017382:Reactive Oxygen Species; D019335:Nitroarginine; D009568:Nitrendipine; D002118:Calcium