Nullification of a positive correlation between urinary levels of alpha 1-microglobulin and ulinastatin by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice.

The relationships between urinary levels of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) were investigated in C57BL/6J mice, a species which reportedly possesses the gene similar to that of humans for synthesizing the precursor protein of alpha 1M and UT. A positive correlation was established in normal mice. However, repetitive administrations (20 mg/kg, IP, four administrations/12 h) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nullified the positive correlation. A similar phenomenon was induced by ICV-administered MPTP (18 and 36 micrograms) in the animals. Furthermore, L-dopa administration (50 mg/kg, IV) in MPTP-treated (1 week after the final IP administration of MPTP) mice reversed the tendency of MPTP, although the agent alone did not affect the positive correlation in normal mice. These results suggest that nullification of the positive correlation probably was induced by the central effects of MPTP. We have found previously that the lack of a positive correlation between urinary levels of alpha 1M and UT distinguishes Parkinson's disease from other neuropsychiatric diseases such as dementia (Alzheimer-type and vascular dementia), schizophrenia and mood disorders. Our present results displayed a phenomenon that the lack of correlation between urinary levels of alpha 1M and UT in patients with Parkinson's disease is reproducible in MPTP-treated mice.