title: Regulation of opioid and cannabinoid receptor genes in human neuroblastoma and T cells by the epigenetic modifiers trichostatin A and 5-aza-2'-deoxycytidine.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of the epigenetic modifiers trichostatin A and 5-aza-2'-deoxycytidine on the expression of the cannabinoid receptors CB1 and CB2 and μ-opioid receptors in human SH SY5Y neuroblastoma cells and human Jurkat T lymphocytes.
  
  
  METHODS
  Using quantitative real-time RT-PCR, mRNA specific for the aforementioned receptors was determined. The functionality of the induced receptors was determined by analyzing the effect of the ligands to regulate intracellular cAMP.
  
  
  RESULTS
  We demonstrated that treatment of SH SY5Y cells, which endogenously express μ-opioid receptors and CB1, but not CB2, resulted in de novo induction of CB2, while mRNA levels of CB1 and μ-opioid receptors were not significantly altered. In contrast, treatment of Jurkat lymphocytes, which endogenously express CB2, but not CB1 and μ-opioid receptors, resulted in de novo induction of CB1 and μ-opioid receptors, while mRNA levels of CB2 were not significantly altered. Furthermore, the functionality of the induced μ-opioid receptors and CB1 in the Jurkat cells was demonstrated.
  
  
  CONCLUSIONS
  Our data suggest an epigenetically regulated expression of cannabinoid receptors and μ-opioid receptors. Their induction by epigenetic modifiers in distinct cells of the nervous and immune system might result in increased effects of the cognate drugs on neuronal and immune functions. Such modifications might be useful for novel therapies for various disorders, e.g. multiple sclerosis, where the elevated transmission of cannabinoid or opioid signals is beneficial.
authors.affiliation: Department of Pharmacology and Toxicology, University of Magdeburg, Magdeburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Börner
authors.forename: Elisa
authors.initials: E
authors.lastname: Martella
authors.forename: Volker
authors.initials: V
authors.lastname: Höllt
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kraus
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D000077209:Decitabine; D044127:Epigenesis, Genetic; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D019169:Jurkat Cells; D009447:Neuroblastoma / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D006877:Hydroxamic Acids; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D017450:Receptors, Opioid, mu; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine