Serotoninergic modulation of cell volume response to estramustine: an image-analysis study on perifused individual glioma cells

A technique of microscopy with computerised detection of early morphologica l changes during continuous perifusion was used to monitor the geometry cha nges of cultured glioma cells (MG-251) when exposed to 40 mg/L estramustine phosphate (EMP) alone or in combination with granisetron (0.1 mu mol/L), o ndansetron (0.1 mu mol/L), or serotonin (1 mu mol/L). When the cells were e xposed to EMP, cell volume measured as projected cell area (PCA) rapidly in creased. Serotonin and ondansetron, but not granisetron, prevented the acut e EMP response (PCA). Serotonin, but none of the 5-HT3 receptor antagonists , protected against the cytotoxicity of EMP to the glioma cells as measured by a fluorometric microculture assay. Our results demonstrate hitherto unk nown differences between selective 5-HT3 receptor antagonist on the cellula r response to EMP and shows the necessity to study the receptor antagonists from viewpoint of interference with the antitumour drug effects on maligna nt cells. The perifusion technique could be used to study the effects of se rotoninergic agonists and antagonists on cell volume regulation of cells ex posed to anticancer drugs. (C) 1999 Elsevier Science Ltd. All rights reserv ed.