Expression of catechol-O-methyltransferase in the brain and periphery of normal and MPTP-treated common marmosets.
Catechol-O-methyltransferase (COMT) inhibition is widely used to potentiate the effects of levodopa in Parkinson's disease but the effects of nigral dopaminergic cell loss and levodopa treatment on COMT activity are not known. The present study investigated the expression of COMT in the brain and liver of normal common marmosets, and animals treated with MPTP and those treated with levodopa to induce dyskinesia. Reverse transcript PCR demonstrated the expression of COMT mRNA in the liver, cortex and striatum of normal marmosets. Using Western blotting, the presence of two subunits of COMT protein, membrane bound COMT (MB-COMT) and soluble COMT (S-COMT), was shown in the liver, cortex and striatum of normal marmosets. Quantitative analysis of the MB-COMT and S-COMT subunit bands showed that there was no significant difference in the density of bands in MPTP treated marmosets or those exposed to levodopa compared to normal animals. COMT immunoreactivity was expressed in many brain regions including the cortex and striatum. No difference in COMT staining intensity was observed between normal, MPTP exposed or MPTP plus levodopa treated animals. COMT immunostaining was present in most striatal neurones and it was occasionally seen in glial cells. The data from present study demonstrated the expression of COMT mRNA and protein in the brain of common marmoset contrary to a previous report that it is not expressed in this species. COMT activity appears unaffected by loss of the dopaminergic nigro-striatal pathway and levodopa treatment.
Zeng
Bai-Yun
BY
Neurodegenerative Disease Research Group, School of Biomedical and Health Sciences, King's College, London, SE1 1UL, UK. b.zeng@kcl.ac.uk
Balfour
Robert H
RH
Jackson
Mike J
MJ
Rose
Sarah
S
Jenner
Peter
P
D000818:Animals; D000978:Antiparkinson Agents / Q000633:toxicity; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D002144:Callithrix; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004409:Dyskinesia, Drug-Induced / Q000201:enzymology; D005260:Female; D007980:Levodopa / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D020267:MPTP Poisoning / Q000201:enzymology*; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism
D000978:Antiparkinson Agents; D012333:RNA, Messenger; D007980:Levodopa; D002394:Catechol O-Methyltransferase