sigma(2) Receptors regulate changes in sphingolipid levels in breast tumor cells |
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Authors: | Crawford Keith W Coop Andrew Bowen Wayne D |
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Institution: | Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA. |
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Abstract: | sigma(2) 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 sigma(2) 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 (3)H]ceramide, with concomitant decreases in (3)H]sphingomyelin. Both effects were attenuated by the novel sigma(2) receptor antagonist, N-phenethylpiperidine oxalate (AC927). sigma(2) Receptors may produce effects on cell growth and apoptosis by regulating the sphingolipid pathway. |
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