Document Detail


Newly identified structurally disparate modulators of osmosensitive taurine efflux inhibit cell cycle progression.
MedLine Citation:
PMID:  12921860     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
FACS analysis and [14C]-taurine efflux were used to determine whether activation of the volume-sensitive organic osmolyte/anion channel plays a role in cell cycle progression. This was achieved by examining the effects of a collection of (i) H(1) antagonists and tricyclic antidepressants with a known inhibitory effect on cell cycle progression, and (ii) antidepressants and oestrogen receptor modulators with molecular structures likely to confer inhibition of the volume-sensitive organic osmolyte/anion channel. Of the 13 compounds examined in this study, the following showed no cytotoxicity following a 48-h exposure, and specifically inhibited osmosensitive taurine efflux (over lactate transport and anion exchange) with IC(50) values of (in microM): fluoxetine, approximately 14; fluvoxamine, approximately 24; amitriptyline, approximately 32; imipramine, approximately 32; mianserin, approximately 40. A 48-h application of these compounds at these concentrations significantly increased arrest in the G0/1 stage of the cell cycle by approximately 10%. The uniformity and specificity of the response elicited by these compounds strongly reinforces a correlation between cell cycle progression and osmosensitive taurine efflux activation.
Authors:
Mark J Belsey; Steven J Culliford; Richard M Morley; Harry J Witchel; Roland Z Kozlowski
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  474     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-08-18     Completed Date:  2004-04-23     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  185-93     Citation Subset:  IM    
Affiliation:
School of Medical Sciences, University of Bristol, University Walk, BS8 1TD Bristol, UK.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle / drug effects,  physiology*
Dose-Response Relationship, Drug
Hela Cells
Humans
Pharmaceutical Preparations / chemistry*
Structure-Activity Relationship
Taurine / antagonists & inhibitors*,  metabolism,  secretion*
Water-Electrolyte Balance / drug effects,  physiology*
Chemical
Reg. No./Substance:
0/Pharmaceutical Preparations; 107-35-7/Taurine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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