title: Expression levels of OPRM1 and PDYN in human SH-SY5Y cells treated with morphine and methadone.
abstract: OBJECTIVE
  The opioid receptor mu-1 (OPRM1, site of action for methadone and morphine, OMIM: 600018) and prodynorphin (PDYN, OMIM: 131340) genes are belonging to the endogenous opioid family. There is no data on alterations of mRNA levels of PDYN and OPRM1 in cells exposed to methadone. Therefore, the present study was carried out.
  
  
  METHODS
  Here we have investigated the alterations of the expression levels of OPRM1 and PDYN genes in response to methadone (final concentrations 1, 2.5, 5, 7.5, 10 μM) and morphine (final concentrations 1, 5, 10 μM) in human SH-SY5Y cells (at 1h, 24h, 72 h, 18 days of exposure times).
  
  
  RESULTS
  The most important findings are summaries as follow: 1) In the cells treated with morphine, the mRNA level of OPRM1 significantly decreased from 1h to 72 h in a dose dependent manner, but it is increased when the cells treated for 18 days by high concentrations of morphine; 2) Although the PDYN mRNA level is increased at 1 and 24h (for 5 and 10 μM morphine), it is decreased at 72 h and 18 days; 3) The mRNA level of OPRM1 negatively is associated with a methadone dose dependent and exposure time dependent manner; 4) In overall, the PDYN mRNA level is increased in the treated cells without any obvious trend by dose of methadone or exposure time.
  
  
  CONCLUSIONS
  Decreasing the PDYN mRNA levels in cells exposed to morphine for long period times, and increasing the level of PDYN mRNA in methadone treated cells, can interpret why heroine-dependent persons, easily accept methadone therapy.
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71467-13565, Iran.
authors.forename: Khyber
authors.initials: K
authors.lastname: Saify
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71467-13565, Iran. Electronic address: saadat@shirazu.ac.ir.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Saadat
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008691:Methadone / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; D004745:Enkephalins; C485764:OPRM1 protein, human; D011498:Protein Precursors; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D009020:Morphine; C033660:preproenkephalin; D008691:Methadone
keywords: Gene expression; Methadone; Morphine; OPRM1; PDYN