Proconvulsive effects of the mitochondrial respiratory chain inhibitor--3-nitropropionic acid.
The role of impaired mitochondrial function in processes leading to the generation of seizures was studied in mice. An inhibitor of mitochondrial complex III, 3-nitropropionic acid, which is known to evoke convulsions per se, and was used here in subthreshold dose, enhanced seizures generated by electric current and application of 4-aminopyridine. In contrast, 3-nitropropionic acid did not affect convulsions induced by gamma-aminobutyric acid (GABA) receptor antagonists - bicuculline, pentylenetetrazol and picrotoxin, glycine antagonist - strychnine, cholinomimetic drug-pilocarpine, and kynurenine aminotransferase inhibitor - aminooxyacetic acid. It is hypothesised that deranged mitochondrial metabolism renders the central nervous system more susceptible to factors inducing seizures via direct depolarization.
Haberek
G
G
Department of Pharmacology and Toxicology, Medical University, Jaczewskiego 8, 20-090, Lublin, Poland.
Tomczyk
T
T
Zuchora
B
B
Wielosz
M
M
Turski
W A
WA
Urbanska
E M
EM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003292:Convulsants / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004579:Electron Transport / Q000187:drug effects*; D004597:Electroshock; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology; D007736:Kynurenic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D009574:Nitro Compounds; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D009574:Nitro Compounds; D015221:Potassium Channels; D011422:Propionates; D005680:gamma-Aminobutyric Acid; D007736:Kynurenic Acid; D000109:Acetylcholine; C015392:3-nitropropionic acid; D005998:Glycine