Dopamine metabolism and free-radical related mitochondrial injury during transient brain ischemia in gerbils.
Regional extracellular release of dopamine (DA) and its metabolites, 3,4-dihydroxy-phenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) was measured in gerbils (with or without pargyline pretreatment) subjected to bilateral carotid artery occlusion (15 min) and various periods of recirculation (up to 6 hr), utilizing intracerebral microdialysis and high-performance liquid chromatography (HPLC) with electrochemical detection. Mitochondrial monoamine oxidase (MAO) and superoxide dismutase (SOD) activities and in vitro stimulated lipid peroxidation (TBARM) were determined in separate experimental groups of animals. The ischemically induced DA release, decrease of MAO-derived DA metabolites DOPAC and HVA, and accumulation of 3-MT were potentiated and prolonged by pargyline pretreatment. Mitochondrial MAO and SOD activities were significantly reduced during ischemia alone and up to 1 hr of reperfusion, whereas TBARM was enhanced during reflow only. The data suggest that reduced activity of mitochondrial antioxidative enzyme(s) but not DA metabolism by MAO may contribute to free radical-mediated injury of (mitochondrial) membranes.
Ishii
H
H
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Stanimirovic
D B
DB
Chang
C J
CJ
Mrsulja
B B
BB
Spatz
M
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D005609:Free Radicals; D005849:Gerbillinae; D006719:Homovanillic Acid / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D015102:3,4-Dihydroxyphenylacetic Acid; D010293:Pargyline; D013482:Superoxide Dismutase; D008995:Monoamine Oxidase; C001746:3-methoxytyramine; D004298:Dopamine; D006719:Homovanillic Acid