σ₂ Receptors regulate changes in sphingolipid levels in breast tumor cells

σ₂ Receptors induce apoptosis in various cell types. The sphingolipid, ceramide as well as the sphingoid bases are involved in cell proliferation. Sphingolipids of MCF-7/Adr- and T47D breast tumor cells were metabolically radiolabeled. The σ₂ receptor agonists (+)-1R,5R-E-8-(3,4-dichlorobenzylidene)-5-(3-hydroxyphenyl)-2-methylmorphan- 7-one (CB-184) and 1S,2R-(-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)- cyclohexylamine (BD737) caused dose-dependent increases in [³H]ceramide, with concomitant decreases in [³H]sphingomyelin. Both effects were attenuated by the novel σ₂ receptor antagonist, N-phenethylpiperidine oxalate (AC927). σ₂ Receptors may produce effects on cell growth and apoptosis by regulating the sphingolipid pathway.