Multipoint analysis of reduced (125)I-meta-iodobenzylguanidine uptake and norepinephrine turnover in the hearts of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine-induced parkinsonism.
BACKGROUND
(125)I-Meta-iodobenzylguanidine (MIBG) cardiac uptake is reduced in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP)-induced parkinsonism, although the cause of disturbance of norepinephrine (NE) turnover is unclear.


METHODS
C57BL6 mice (15 weeks old) were divided into six groups (n=14 each) according to the timing of MPTP injection (40 mg/kg) before (125)I-MIBG: Group A, control (no MPTP injection); Group B, 1 day; Group C, 4 days; Group D, 7 days; Group E, 21 days; Group F, 7, 14 and 21 days. (125)I-MIBG (0.185 MBq) was injected and the cardiac percentage injected dose per gram of tissue (%ID/g), dopamine (DA) and NE concentrations were measured. The cardiac maximal binding potential (B(max)) of NE transporter (NET) was also calculated in 20 mice per group.


RESULTS
The %ID/g of B, C, D, E and F mice were significantly lower than in A; those of C, D and E were significantly higher than in B; and that of F was significantly lower than in E. The DA concentrations were similar among all groups. The NE concentrations of B, C and F mice were significantly lower than in A, while those of C, D, E and F were significantly higher than in B, and that of F was significantly lower than in E. The B(max) of NET in B was significantly lower than in A.


CONCLUSIONS
Thus, MPTP causes rapid reductions in cardiac (125)I-MIBG uptake and B(max) of NET, followed by partial recovery of (125)I-MIBG uptake. Changes in cardiac (125)I-MIBG uptake and NE turnover were closely related in postganglionic cardiac sympathetic nerve terminals in mice with MPTP-induced parkinsonism.
Fukumitsu
Nobuyoshi
N
Proton Medical Research Center, University of Tsukuba, Tsukuba 305-8575, Japan. fukumitsun@yahoo.co.jp
Suzuki
Masahiko
M
Fukuda
Takahiro
T
Kiyono
Yasushi
Y
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D019797:3-Iodobenzylguanidine / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D017072:Neostriatum / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism*; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D050484:Norepinephrine Plasma Membrane Transport Proteins; D019797:3-Iodobenzylguanidine; D014443:Tyrosine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D009638:Norepinephrine