L-deprenyl induces aromatic L-amino acid decarboxylase (AADC) mRNA in the rat substantia nigra and ventral tegmentum. An in situ hybridization study.
L-Deprenyl is a complex drug, and number of mechanisms have been proposed to explain its effects. These include blockade of dopamine metabolism, amplification of dopamine responses, induction of superoxide dismutase or delaying apoptosis. Using in situ hybridization techniques, we have shown that L-deprenyl (5-10 mg/kg intraperitoneally, killed after 24 h) increases aromatic L-amino acid decarboxylase (AADC) mRNA levels in rat substantia nigraventral tegmental area. In human brain tissue, AADC is present at low levels, suggesting a possible rate-limiting role in monoamine synthesis. This is particularly important in parkinsonian patients, since the therapeutic efficacy of L-DOPA is attributed to its enzymatic decarboxylation to dopamine. The present findings support that one of the effects of L-deprenyl may be to facilitate the decarboxylation of L-DOPA by increasing the availability of AADC.
Li
X M
XM
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
Juorio
A V
AV
Qi
J
J
Boulton
A A
AA
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics*; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D017403:In Situ Hybridization; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*; D013378:Substantia Nigra / Q000201:enzymology*; D013681:Tegmentum Mesencephali / Q000201:enzymology*; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D012642:Selegiline; D007980:Levodopa; D001142:Aromatic-L-Amino-Acid Decarboxylases