The role of lipid peroxidation in the possible involvement of membrane-bound monoamine oxidases in gamma-aminobutyric acid and glucosamine deamination in rat brain. Focus on chemical pathogenesis of experimental audiogenic epilepsy.
Incubation of rat brain synaptosomes and mitochondria with LPO inducers (Fe2+ and ascorbate) was accompanied by a decrease of deamination of serotonin (substrate of MAO-A) in mitochondria, but not in synaptosomes, with simultaneous stimulation of GABA and GLCA deamination, apparently owing to modification of catalytic properties of brain membrane-bound MAO. Oxidation of PEA (substrate of MAO-B) was insignificantly altered in both fractions. Reactions of deamination of serotonin, GABA, and GLCA (but not PEA), were highly sensitive to a selective inhibitor of MAO-A pyrazidol (pyrlindole). Isoniazid and hydrazides of quinoline carbonic acids (inhibitors of both modified MAO and copper-containing amine oxidases) strongly inhibited deamination of GABA and GLCA. During epileptiformic seizures in rats, genetically selected for high incidence of audiogenic epilepsia, stimulation in brain synaptosomes and mitochondria of LPO was observed. This was accompanied by a marked decrease in serotonin and PEA deamination, with a simultaneous increase in GABA and GLCA deamination in both fractions. The data obtained suggest that appearance of GABA-deaminating activity owing to modification of catalytic properties of MAO, might be an essential pathogenetic component in the development of epileptic seizures.
Medvedev
A E
AE
Institute of Biological and Medical Chemistry, Academy of Medical Sciences of the USSR, Moscow.
Rajgorodskaya
D I
DI
Gorkin
V Z
VZ
Fedotova
I B
IB
Semiokhina
A F
AF
D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D002227:Carbazoles / Q000494:pharmacology; D003641:Deamination; D004829:Epilepsy, Generalized / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D005944:Glucosamine / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology; D015227:Lipid Peroxidation; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009928:Organ Specificity; D010100:Oxygen / Q000378:metabolism; D010627:Phenethylamines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics; D011922:Rats, Mutant Strains / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002227:Carbazoles; D008563:Membrane Lipids; D008565:Membrane Proteins; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; C029261:phenethylamine; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D007501:Iron; D008995:Monoamine Oxidase; D005944:Glucosamine; D001205:Ascorbic Acid; D010100:Oxygen; C009830:pirlindole