Reduction in number of dopamine uptake sites but unchanged number of piperazine-acceptor/CYP450IID6 binding sites in the human caudate nucleus in aging.
A substantial decrease in number of striatal dopamine uptake sites is a characteristic finding in aging. This decrease resembles the dopaminergic nigro-striatal degeneration in Parkinson's disease (PD). A dysfunction of cytochrome P450IID6 (debrisoquine-4-hydroxylase) is suggested to be involved in the pathogenesis of PD. In this study, binding sites associated with the neuronal form of P450IID6 were studied in the caudate nucleus from individuals in the age range 20-81 years using [3H]GBR 12935 as a radioligand. No significant changes in binding parameters were obtained, while in the same region a significant decrease in number of dopamine uptake sites occurred. Thus, in aging, P450IID6 and dopaminergic degeneration seem not to be functionally related in this region. Whether such a relation exists in PD is still to be examined.
Norlén
M
M
Department of Geriatric Medicine, Umeå University, Sweden.
Allard
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D001665:Binding Sites; D002421:Caudate Nucleus / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000502:physiology; D009474:Neurons / Q000502:physiology; D010879:Piperazines / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D013816:Thermodynamics
D010879:Piperazines; D011954:Receptors, Dopamine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D019389:Cytochrome P-450 CYP2D6