Effect of tricyclic antidepressants on sphingomyelinase and other sphingolipid hydrolases in C6 cultured glioma cells.
Cationic amphiphilic drugs, which include tricyclic antidepressants, have been shown to give rise to lipidoses under experimental conditions, with a general increase of lipids especially phospholipids. We report here an early and important decrease in sphingomyelinase activity in C6 glioma cells cultured in the presence of imipramine or desipramine at final concentrations of 0.01 and 0.05 mM. The effect was both dose-dependent and time-dependent and was observed before any lipid accumulation. Cerebroside beta-glucosidase and cerebroside beta-galactosidase had normal activities under the same experimental conditions and thus there was no general effect on membrane-bound sphingolipid hydrolases. A decrease of sphingomyelinase activity has been previously reported for two amphiphilic compounds, perhexiline maleate and AY 9944. These results suggest a potential function of sphingomyelinase in the mode of action of these drugs.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001932:Brain Neoplasms / Q000201:enzymology*; D046508:Culture Techniques; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000378:metabolism; D005910:Glioma / Q000201:enzymology*; D007099:Imipramine / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000201:enzymology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D013107:Sphingolipids / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*
D004798:Enzymes; D013107:Sphingolipids; D010727:Phosphoric Diester Hydrolases; D013108:Sphingomyelin Phosphodiesterase; D007099:Imipramine; D003891:Desipramine