Nullification of a positive correlation between urinary contents of alpha1-microglobulin and ulinastatin with intracerebroventricularly administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+) in mice.
Striatal dopamine contents in C57BL/6J mice were reduced at 24 h after intracerebroventricular (ICV) administration of 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+) in a dose-dependent manner. A dose of 1.8 microg MPP+ significantly (P < 0.05) suppressed the dopamine contents, whereas a similar dose of MPTP did not. A definite positive correlation between urinary contents of alpha1-microglobulin (alpha1M) and ulinastatin (UT) existed in normal mice. However, this correlation was nullified by ICV administration of 18 and 36 microg MPTP or 1.8 and 18 microg MPP+. With 1.8 microg MPTP, a positive correlation between urinary contents of alpha1M and UT was displayed. The urine volume, creatinine content, glomerular filtration rate, alpha1M and UT contents, and alpha1M/UT ratio of urine collected for 24 h post-ICV administration of MPTP or MPP+, were not statistically different from those of control mice. Our findings suggest that the central effects of MPP+, a neurotoxic metabolite of MPTP, nullify the positive correlation between urinary contents of alpha1M and UT without affecting renal functions.
Kaku
K
K
Department of Psychiatry, Shimane Medical University, Izumo, Japan.
Shikimi
T
T
Kamisaki
Y
Y
Inagaki
T
T
Ishino
H
H
Okunishi
H
H
Takaori
S
S
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000510:Alpha-Globulins / Q000652:urine*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D006023:Glycoproteins / Q000652:urine*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism
D000510:Alpha-Globulins; D006023:Glycoproteins; C016001:alpha-1-microglobulin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C028665:urinastatin; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine