MPP+-induced efflux of dopamine and lactate from rat striatum have similar time courses as shown by in vivo brain dialysis.
Perfusion of rat striatum with 10 mM 1-methyl-4-phenylpyridinium (MPP+) during 1 min caused a rapid reversible increase in dopamine (DA) efflux (maximal after 4 min) that was similar to the effects of 1 or 15 min 10 mM amphetamine. A massive, prolonged, and irreversible release of DA occurred after 15 min 10 mM MPP+, showing a biphasic trend: the rapid amphetamine-like increase was followed by a slower and larger DA efflux, reaching its maximum after 25 min. One minute perfusions with 1-100 mM MPP+ caused a gradual increase in the overflow of striatal lactate, reaching a maximum effect after 20-30 min. The similarity between the time courses of the MPP+-induced efflux of DA and lactate suggests that both effects are probably consequences of inhibition of aerobic glycolysis by MPP+. A comparison with the courses of DA and lactate efflux after death of control rats showed a delay of several minutes before the toxic effects of MPP+ become apparent. These in vivo data are consistent with the hypothesis that MPP+ accumulates and then kills dopaminergic cells, possibly by the irreversible inhibition of mitochondrial respiration.
Rollema
H
H
Department of Medicinal Chemistry, State University Groningen, The Netherlands.
Kuhr
W G
WG
Kranenborg
G
G
De Vries
J
J
Van den Berg
C
C
D015655:1-Methyl-4-phenylpyridinium; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007773:Lactates; D011726:Pyridinium Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; D019344:Lactic Acid; D006897:Hydroxyindoleacetic Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D006719:Homovanillic Acid