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Neurochemical Research

, Volume 24, Issue 1, pp 69–78 | Cite as

U18666A Inhibits Intracellular Cholesterol Transport and Neurotransmitter Release in Human Neuroblastoma Cells

  • Susan M. Sparrow
  • Jodi M. Carter
  • Neale D. Ridgway
  • Harold W. Cook
  • David M. Byers
Article

Abstract

To determine if neurochemical function might be impaired in cell models with altered cholesterol balance, we studied the effects of U18666A (3-β-[(2-diethyl-amino)ethoxy]androst-5-en-17-one) on intracellular cholesterol metabolism in three human neuroblastoma cell lines (SK-N-SH, SK-N-MC, and SH-SY5Y). U18666A (≤0.2 μg/ml) completely inhibited low density lipoprotein (LDL)-stimulated cholesterol esterification in SK-N-SH cells, while cholesterol esterification stimulated by 25-hydroxycholesterol or bacterial sphingomyelinase was unaffected or partially inhibited, respectively. U18666A also blocked LDL-stimulated downregulation of LDL receptor and caused lysosomal accumulation of cholesterol as measured by filipin staining. U18666A treatment for 18 h resulted in 70% inhibition of K+-evoked norepinephrine release in phorbol esterdifferentiated SH-SY5Y cells, while release stimulated by the calcium ionophore A23187 was only slightly affected. These results suggest that U18666A may preferentially block a voltage-regulated Ca2+ channel involved in norepinephrine release and that alterations in neurotransmitter secretion might be a feature of disorders such as Niemann-Pick Type C, in which intracellular cholesterol transport and distribution are impaired.

Cholesterol U18666A neuroblastoma SH-SY5Y Niemann-Pick C disease norepinephrine 

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Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Susan M. Sparrow
    • 1
  • Jodi M. Carter
    • 1
  • Neale D. Ridgway
    • 1
  • Harold W. Cook
    • 1
  • David M. Byers
    • 1
  1. 1.Atlantic Research Centre, Departments of Pediatrics and BiochemistryDalhousie UniversityHalifaxCanada

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