Reduced 125I-meta-iodobenzylguanidine uptake and norepinephrine transporter density in the hearts of mice with MPTP-induced parkinsonism.
Uptake of (123)I-meta-iodobenzylguanidine ((123)I-MIBG) is markedly reduced in the hearts of patients with Parkinson's disease. Although the mechanism of this reduction is unclear, (12)(5)I-MIBG uptake is similarly reduced in the hearts of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP)-induced parkinsonism. Three groups of ten 15-week-old C57BL6 mice received intraperitoneal injections of (1) saline (control), (2) 10 mg/kg MPTP or (3) 40 mg/kg MPTP. After 0.185 MBq of (125)I-MIBG was injected, the percent injected dose of (125)I-MIBG per gram of tissue (%ID/g) was determined and cardiac concentrations of norepinephrine were measured. Cardiac concentrations of norepinephrine transporter (NET) were measured in three groups of twenty 15-week-old C57BL6 mice receiving these same treatments. The %ID/g in mice receiving 10 or 40 mg/kg MPTP (5.7 +/- 1.1 and 4.4 +/- 1.2%/g) was significantly lower than that in control mice (11.3 +/- 2.2%/g; P < .00001 and P < .0000001, respectively). The norepinephrine concentration in mice receiving 10 or 40 mg/kg MPTP (7.86 +/- 0.67 x 10(5) and 7.50 +/- 0.89 x 10(5) pg/wet g) was significantly lower than that in control mice (9.21 +/- 0.97 x 10(5) pg/wet g; P < .01 and P < .001, respectively). The NET density in mice receiving 10 or 40 mg/kg MPTP (81 +/- 12, 61 +/- 7 fmol/mg protein) was significantly lower than that in control mice (126 +/- 7 fmol/mg protein; P < .000001 and P < .0000001, respectively). The %ID/g of (125)I-MIBG and NET density decreased as the dose of MPTP increased. This study clearly shows that reduced cardiac (12)(5)I-MIBG uptake in mice with MPTP-induced parkinsonism is closely related to the reduced NET density in postganglionic cardiac sympathetic nerve terminals.
Fukumitsu
Nobuyoshi
N
Proton Medical Research Center, University of Tsukuba, Ibaragi, Japan. gzll3162@nifty.ne.jp
Suzuki
Masahiko
M
Fukuda
Takahiro
T
Kiyono
Yasushi
Y
Kajiyama
Satomi
S
Saji
Hideo
H
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000000981:diagnostic imaging* / Q000187:drug effects*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution / Q000187:drug effects
D050484:Norepinephrine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine