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21‐Aminosteroids Interact with the Dopamine Transporter to Protect Against 1‐Methyl‐4‐Phenylpyridinium‐Induced Neurotoxicity
Author(s) -
SanchezRamos Juan R.,
Song Shije,
Mash Deborah C.,
Weiner William J.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09314.x
Subject(s) - neurotoxin , neurotoxicity , dopamine transporter , mazindol , chemistry , transporter , dopamine , pharmacology , dopamine plasma membrane transport proteins , neuron , biochemistry , toxicity , biology , endocrinology , neuroscience , organic chemistry , gene
U‐78518F, a 21‐aminosteroid from the novel family of lipid peroxidation inhibitors (lazaroids), increased survival of dopamine (DA) neurons in mesencephalic cell cultures incubated with the neurotoxin l ‐methyl‐4‐phenylpyridinium (MPP + ). Protection against DA neuron death occurred with increasing concentrations of U‐78518F up to 30 μ M . Nonspecific toxicity produced with higher concentrations of MPP + was not affected by the lazaroid. U‐78518F inhibited cellular uptake of [ 3 H]MPP + and [ 3 H]DA, but not that of γ‐[ 3 H]aminobutyric acid. In human striatal membrane preparations, U‐78518F competed with [ 3 H]mazindol for binding to the DA transporter, with a calculated K i value of 10 μ M . Two of four lazaroids tested inhibited [ 3 H]DA uptake in the cell culture system. The protective effects of 21‐aminosteroids in MPP + ‐induced neurotoxicity are, in part, a function of the interaction of these agents with the DA transporter.