Studies of aminochrome toxicity in a mouse derived neuronal cell line: is this toxicity mediated via glutamate transmission?
Aminochrome was found to be toxic in a mouse-derived neuronal cell line (CNh). The effect was concentration dependent (10-150microM). The issue whether aminochrome toxicity involves glutamate transmission was studied with several glutamate receptors antagonists. Incubation of the cells with aminochrome (150microM) in the presence of 100microM of the AMPA antagonist, NBQX resulted in an increase of cell survival, from 52 to 73%. However, this protective effect did not seem to be related to activation of ionotropic glutamate receptors since incubation of CNh cells with 200microM of glutamate resulted in only 10% decrease of cell survival. However, NBQX was found to inhibit in vitro the autoxidation process. One hundred microM AP-5 did not have any effect on aminochrome toxicity. The toxic effect of aminochrome on CNh cells seems to be dependent of extracellular activation since addition of dicoumarol, a specific inhibitor of DT-diaphorase, did not affect that toxicity, which can be explained perhaps by a lack of a transport system for aminochrome into the CNh cells.
Arriagada
C
C
Program of Molecular and Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Santiago.
Dagnino-Subiabre
A
A
Caviedes
P
P
Armero
J M
JM
Caviedes
R
R
Segura-Aguilar
J
J
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D001728:Dicumarol / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D045563:Indolequinones; D007211:Indoles / Q000633:toxicity*; D051379:Mice; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D011810:Quinoxalines / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D045563:Indolequinones; D007211:Indoles; D011810:Quinoxalines; D017470:Receptors, Glutamate; D014475:Uncoupling Agents; D009243:NAD; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C091584:aminochrome 1; D018698:Glutamic Acid; D001728:Dicumarol; D002374:Catalase; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); D004298:Dopamine