Increase of ATP levels by glutamate antagonists is unrelated to neuroprotection.
Succinic dehydrogenase in mouse cortical explant cultures was inhibited by 3-nitropropionic acid (3-NPA). ATP concentrations declined upon application of 3-NPA. At 4 h, ATP levels of cultures treated with 3-NPA alone were no different from those in cultures treated additionally with MK-801 (20 microM), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) or a combination thereof. However, MK-801 and MK-801 plus CNQX mitigated morphological lesions caused by 3-NPA. CNQX alone did not influence the extent of morphological damage. In conclusion, MK-801, at concentrations which were neuroprotective against 3-NPA lesions in cortical explant cultures, did not modify 3-NPA dependent decreases in cellular ATP levels. These data indicate that the neuroprotective effects of glutamate receptor antagonists in this model are probably receptor mediated and do not involve effects on cellular metabolism.
Riepe
M
M
Center for Research on Occupational and Environmental Toxicology, Portland, OR.
Ludolph
A
A
Seelig
M
M
Spencer
P S
PS
Ludolph
A C
AC
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D046508:Culture Techniques; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D051379:Mice; D009410:Nerve Degeneration / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology; D009574:Nitro Compounds; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010936:Plant Extracts; D011422:Propionates / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D009574:Nitro Compounds; D010936:Plant Extracts; D011422:Propionates; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000255:Adenosine Triphosphate; C015392:3-nitropropionic acid