title: Nimodipine and flunarizine have different effects on survival and morphology of PC12 cells during nerve growth factor deprivation.
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.
authors.affiliation: Department of Biochemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Dispersyn
authors.forename: R
authors.initials: R
authors.lastname: Nuydens
authors.forename: M
authors.initials: M
authors.lastname: Borgers
authors.forename: H
authors.initials: H
authors.lastname: Geerts
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005444:Flunarizine / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology*; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats
chemical_list: D002121:Calcium Channel Blockers; D002614:Chelating Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D009553:Nimodipine; D020932:Nerve Growth Factor; D005444:Flunarizine; D002118:Calcium