Document Detail


Verapamil inhibits proliferation, migration and protein kinase C activity in human retinal pigment epithelial cells.
MedLine Citation:
PMID:  9702177     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of three calcium channel blockers, verapamil, diltiazem and nifedipine, were examined on in vitro proliferation and migration of human retinal pigment epithelial cells. Human retinal pigment epithelial cells were seeded in Dulbecco's modified essential medium with 10% fetal bovine serum and different concentrations of the three calcium channel blockers. After 3 days of treatment, cell proliferation was determined by cell counting and by [3H]-thymidine uptake. Cell viability was determined with trypan blue exclusion. For determination of cell migration, retinal pigment epithelial cells were grown to confluence and then growth-inhibited with mitomycin C. After a 3 mm zone was denuded, the cells were treated with different concentrations of the calcium channel antagonists. After 24 hr, the cells that had migrated over the wound edge were counted. To determine the involvement of protein kinase C in the verapamil effect, its activity was measured in both verapamil-treated and untreated cells. Verapamil dose dependently inhibited serum-induced proliferation of retinal pigment epithelial cells, when measured by cell number (IC50 14.6 microM) or [3H]-thymidine incorporation (IC50 11.3 microM). At concentrations of 15 microM and below, there was no effect on cell viability, as determined by morphology and trypan blue exclusion. Diltiazem inhibited cell proliferation at a concentration of 100 microM; however, 100 microM nifedipine had no effect. Verapamil showed a significant inhibition of serum-induced migration in the range of 10 microM to 0.1 microM. The IC50 of the inhibition of retinal pigment epithelial cell proliferation and migration by verapamil is significantly higher than that seen for effects on calcium channel blockage. Eight micromolar verapamil reversibly inhibited total protein kinase-C activity in retinal pigment epithelial cells suggesting the possibility that the drug may act by inhibiting the protein kinase-C pathway. These data suggest the potential of the calcium channel blocker verapamil as a pharmacological modulator of disorders such as proliferative vitreoretinopathy in which there is increased retinal pigment epithelial cell proliferation and migration.
Authors:
S Hoffman; R Gopalakrishna; U Gundimeda; T Murata; C Spee; S J Ryan; D R Hinton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental eye research     Volume:  67     ISSN:  0014-4835     ISO Abbreviation:  Exp. Eye Res.     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1998-09-11     Completed Date:  1998-09-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370707     Medline TA:  Exp Eye Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  45-52     Citation Subset:  IM    
Affiliation:
Doheny Eye Institute, Los Angeles, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Calcium Channel Blockers / pharmacology*
Cell Division / drug effects
Cell Movement / drug effects
Cells, Cultured
Depression, Chemical
Diltiazem / pharmacology
Dose-Response Relationship, Drug
Humans
Nifedipine / pharmacology
Pigment Epithelium of Eye / cytology,  drug effects*,  physiology
Protein Kinase C / metabolism*
Verapamil / pharmacology*
Grant Support
ID/Acronym/Agency:
EY01545/EY/NEI NIH HHS; EY03040/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 21829-25-4/Nifedipine; 42399-41-7/Diltiazem; 52-53-9/Verapamil; EC 2.7.11.13/Protein Kinase C

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