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.

INTRODUCTION (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.