title: The effect of mitragynine on cAMP formation and mRNA expression of mu-opioid receptors mediated by chronic morphine treatment in SK-N-SH neuroblastoma cell.
abstract: BACKGROUND
  [corrected] Mitragynine is an indole alkaloid compound of Mitragyna speciosa (M. speciosa) Korth. (Rubiaceae). This plant is native to the southern regions of Thailand and northern regions of Malaysia and is frequently used to manage the withdrawal symptoms in both countries.
  
  
  OBJECTIVE
  To investigate the effect of mitragynine after chronic morphine treatment on cyclic AMP (cAMP) level and mRNA expression of mu-opioid receptor (MOR) in human neuroblastoma SK-N-SH cell.
  
  
  METHODS
  Mitragynine was isolated from the Mitragyna speciosa plant using the acid-base extraction method. The cAMP level upon forskolin stimulation in the cells was determined using the Calbiochem(®) Direct Immunoassay Kit. The mRNA expression of the MOR was carried out using quantitative RT-PCR.
  
  
  RESULTS
  Cotreatment and pretreatment of morphine and mitragynine significantly reduced the production of cAMP level at a lower concentration of mitragynine while the higher concentration of this compound could lead to the development of tolerance and dependence as shown by the increase of the cAMP level production in foskolin stimulation. In MOR mRNA expression study, cotreatment of morphine with mitragynine significantly reduced the down-regulation of MOR mRNA expression as compared to morphine treatment only.
  
  
  CONCLUSIONS
  These finding suggest that mitragynine could possibly avoid the tolerance and dependence on chronic morphine treatment by reducing the up-regulation of cAMP level as well as reducing the down-regulation of MOR at a lower concentration of mitragynine.
authors.affiliation: Malaysian Institute Pharmaceuticals and Nutraceuticals (IPharm), Ministry of Science, Technology and Innovation (MOSTI) Jalan Bukit Gambir, 11700 Gelugor Pulau Pinang, Malaysia.
authors.forename: Mohd Fadzly Amar
authors.initials: MF
authors.lastname: Jamil
authors.forename: Mohd Ferdaues Mohd
authors.initials: MF
authors.lastname: Subki
authors.forename: Tan Mei
authors.initials: TM
authors.lastname: Lan
authors.forename: Mohamed Isa Abdul
authors.initials: MI
authors.lastname: Majid
authors.forename: Mohd Ilham
authors.initials: MI
authors.lastname: Adenan
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D032065:Mitragyna; D009020:Morphine / Q000008:administration & dosage*; D018515:Plant Leaves; D012333:RNA, Messenger / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics*; D046948:Secologanin Tryptamine Alkaloids / Q000008:administration & dosage*; D019966:Substance-Related Disorders; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D000701:Analgesics, Opioid; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D046948:Secologanin Tryptamine Alkaloids; D014212:Tretinoin; D009020:Morphine; D000242:Cyclic AMP; C001801:mitragynine