21‐Aminosteroids Interact with the Dopamine Transporter to Protect Against 1‐Methyl‐4‐Phenylpyridinium‐Induced Neurotoxicity

Juan R. Sanchez‐Ramos, Shije Song, Deborah C. Mash, William J. Weiner

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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 1-methyl-4-phenylpyridinium (MPP+). Protection against DA neuron death occurred with increasing concentrations of U-78518F up to 30 μM Non-specific toxicity produced with higher concentrations of MPP+ was not affected by the lazaroid. U-78518F inhibited cellular uptake of [3H]MPP+ and [3H]DA, but not that of γ-[3H]aminobutyric acid. In human striatal membrane preparations, U-78518F competed with [3H]mazindol for binding to the DA transporter, with a calculated Ki value of 10 μM. Two of four lazaroids tested inhibited [3H]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.

Original languageEnglish (US)
Pages (from-to)328-334
Number of pages7
JournalJournal of neurochemistry
Volume58
Issue number1
DOIs
StatePublished - Jan 1992

Keywords

  • 21-Aminosteroids
  • Dopamine transporter
  • Mesencephalic cell cultures
  • MPP
  • Neurotoxicity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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