Striatal L-dopa decarboxylase activity in Parkinson's disease in vivo: implications for the regulation of dopamine synthesis.
L-DOPA is a large neutral amino acid subject to transport out of, as well as into, brain tissue. Competition between dopamine synthesis and L-DOPA egress from striatum must favor L-DOPA egress if decarboxylation declines relatively more than transport in Parkinson's disease. To test this hypothesis, we injected patients with Parkinson's disease with a radiolabeled analogue of L-DOPA and recorded regional brain radioactivity as a function of time by means of positron emission tomography. We simultaneously estimated the activity of the decarboxylating enzyme and the amino acid transport. In the striatum of patients, we found the L-DOPA decarboxylase activity to be reduced in the head of the caudate nucleus and the putamen. However, the rate of egress of the DOPA analogue was unaffected by the disease and thus inhibited dopamine synthesis more than predicted in the absence of L-DOPA egress.
McConnell Brain Imaging Center, Montreal Neurological Institute, Quebec, Canada.
A
A
Gjedde
G C
GC
Léger
P
P
Cumming
Y
Y
Yasuhara
A C
AC
Evans
M
M
Guttman
H
H
Kuwabara
D003342:Corpus Striatum / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis*; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D008954:Models, Biological; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000201:enzymology*; D014055:Tomography, Emission-Computed
C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase; D004298:Dopamine