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Serotonergic conversion of MPTP and dopaminergic accumulation of MPP +
Author(s) -
Shen R.-S.,
Abell C.W.,
Gessner W.,
Brossi A.
Publication year - 1985
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(85)81028-0
Subject(s) - mptp , nomifensine , serotonergic , dopaminergic , chemistry , dopamine , desipramine , monoamine oxidase , pargyline , imipramine , striatum , serotonin , endocrinology , medicine , pharmacology , biochemistry , biology , antidepressant , hippocampus , enzyme , receptor , alternative medicine , pathology
[ 3 H]MPP + had lower K m and higher V max values for its accumulation in rat brain synaptosomes than did [ 3 H]MPTP. The kinetic parameters favored the uptake of [ 3 H]MPP + in the striatum to that in hypothalamus, whereas they were equally favorable for the uptake of [ 3 H]MPTP in both regions. Hypothalamic uptake of [ 3 H]MPTP and [ 3 H]MPP + was inhibited by desipramine, imipramine, norepinephrine, and serotonin. Striatal uptake of [ 3 H]MPP + and [ 3 H]MPTP was blocked by nomifensine and dopamine. These results support the concept that MPTP accumulates in serotonergic neurons where it is oxidized by monoamine oxidase B to MPP + , which is released and then is selectively accumulated in dopaminergic neurons via the dopamine uptake system.