sigma(2) Receptors regulate changes in sphingolipid levels in breast tumor cells.
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.
Crawford
Keith W
KW
Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA.
Coop
Andrew
A
Bowen
Wayne D
WD
D001597:Benzylidene Compounds / Q000494:pharmacology; D001943:Breast Neoplasms; D002455:Cell Division; D003514:Cyclohexylamines / Q000494:pharmacology; D006801:Humans; D007223:Infant; D009019:Morphinans / Q000494:pharmacology; D010070:Oxalates / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists / Q000502:physiology*; D013109:Sphingomyelins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001597:Benzylidene Compounds; C096583:CB 182; D003514:Cyclohexylamines; D009019:Morphinans; C470324:N-phenethylpiperidine oxalate; D010070:Oxalates; D010880:Piperidines; D011759:Pyrrolidines; D017480:Receptors, sigma; D013109:Sphingomyelins; C075567:BD 737