Nimodipine and flunarizine have different effects on survival and morphology of PC12 cells during nerve growth factor deprivation

Eur J Pharmacol. 1999 Nov 12;384(1):61-70. doi: 10.1016/s0014-2999(99)00665-2.

Abstract

The purpose of this study was to examine the effect of antagonists of different subtypes of Ca(2+) channels (nimodipine and flunarizine) and two types of Ca(2+) chelating agents (the cell permeant Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid acetoxymethylester (BAPTA-AM) and the cell non-permeant Ca(2+) chelator EGTA) on neurite retraction and cell death of nerve growth factor (NGF)-differentiated PC12 cells after NGF deprivation. We demonstrated that flunarizine and nimodipine, but not BAPTA-AM and EGTA, provided protection against cell death due to NGF deprivation. Using time-lapse videomicroscopy and quantitative image analysis, we found that retraction of neurites was an early and fast phenomenon after removal of NGF. None of the compounds tested (flunarizine, nimodipine, BAPTA-AM, EGTA) could prevent the retraction of neurites.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Cell Survival / drug effects*
  • Chelating Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Flunarizine / pharmacology*
  • Nerve Growth Factor / pharmacology*
  • Neurites / drug effects
  • Neurites / physiology
  • Nimodipine / pharmacology*
  • PC12 Cells / cytology
  • PC12 Cells / drug effects
  • PC12 Cells / metabolism
  • Rats

Substances

  • Calcium Channel Blockers
  • Chelating Agents
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Egtazic Acid
  • Nimodipine
  • Nerve Growth Factor
  • Flunarizine
  • Calcium