Newly identified structurally disparate modulators of osmosensitive taurine efflux inhibit cell cycle progression
| Autor: | Roland Z. Kozlowski, Harry J. Witchel, Steven J Culliford, Richard M. Morley, Mark J. Belsey |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Lactate transport Taurine Dose-Response Relationship Drug Cell Cycle Fluvoxamine Water-Electrolyte Balance Cell cycle Structure-Activity Relationship chemistry.chemical_compound Pharmaceutical Preparations chemistry Biochemistry Osmolyte medicine Humans Efflux Cytotoxicity HeLa Cells Tricyclic medicine.drug |
| Zdroj: | European Journal of Pharmacology. 474:185-193 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(03)02073-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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