Slow N-acetyltransferase 2 status leads to enhanced intrastriatal dopamine depletion in 6-hydroxydopamine-lesioned rats.
We previously reported an association between the N-acetyltransferase 2 (NAT2) slow acetylator status and Parkinson's disease (PD). We have now investigated the possible functional relevance of this association by treating Fischer 344 (F344) rapid and Wistar-Kyoto (WKY) slow NAT2 acetylator rat strains with the neurotoxin 6-hydroxydopamine (6-OHDA). Intrastriatal treatment with either 10 or 20 microg of 6-OHDA lead to a significantly greater reduction of striatal dopamine concentrations in the WKY slow acetylator rat strain than in the F344 rapid acetylator rat strain (P < 0.004), reflecting a more marked degree of dopaminergic denervation. Nigral dopaminergic cell counts were also lower in the WKY rats, but this difference failed to reach statistical significance, suggesting that slow acetylation is especially deleterious at the level of striatal nerve endings.
Grundmann
M
M
Department of Neurology, Philipps-University, Marburg, Germany.
Earl
C D
CD
Sautter
J
J
Henze
C
C
Oertel
W H
WH
Bandmann
O
O
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D004298:Dopamine / Q000378:metabolism*; D004351:Drug Resistance / Q000235:genetics; D008297:Male; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001191:Arylamine N-Acetyltransferase; D004298:Dopamine