title: Protective effects of the delta opioid peptide [D-Ala2, D-Leu5]enkephalin in an ex vivo model of ischemia/reperfusion in brain slices.
abstract: BACKGROUND
  The delta opioid peptide [D-Ala2, D-Leu5]enkephalin (DADLE) plays a key role in neuronal protection against both hypoxic and ischemic conditions. However, the cellular mechanisms of action of DADLE under these conditions remain unclear.
  
  
  METHODS
  Ischemia was simulated with perfusing the brain slices with glucose-free artificial cerebrospinal fluid. Apoptosis was examined using an in situ cell death detection kit and expressed as the percentage of positively labeled neurons relative to total number of neurons. PCR was performed by adding cDNA, 5 pm dNTP, 1 μL Taqase, and primers. PCR products were separated with electrophoresis, stained with ethidium bromide, and visualized under ultraviolet light.
  
  
  OBJECTIVE
  To investigate the potential effects of DADLE in an ex vivo model of cerebral ischemia/reperfusion.
  
  
  RESULTS
  DADLE attenuated lactic dehydrogenase release and neuronal apoptosis in a concentration-dependent manner. The protective effects of DADLE were attenuated by representative selective delta2, but not delta1 opioid antagonists. Treatment with PD98059, a selective inhibitor of ERK kinase (MEK), also blocked the protective effect of DADLE as well as ERK phosphorylation induced by DADLE.
  
  
  CONCLUSIONS
  Endogenous opioid peptides could promote cell survival via delta2 opioid receptors, possibly through the downstream MEK-ERK pathway.
authors.affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Zheng
authors.forename: Xiang-Rui
authors.initials: XR
authors.lastname: Wang
authors.forename: Hong-Zhuan
authors.initials: HZ
authors.lastname: Chen
authors.forename: Xing-Jun
authors.initials: XJ
authors.lastname: Wu
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Zhao
authors.forename: Dian-San
authors.initials: DS
authors.lastname: Su
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000187:drug effects; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D018696:Neuroprotective Agents; D017465:Receptors, Opioid, delta; D016308:Enkephalin, Leucine-2-Alanine; D007770:L-Lactate Dehydrogenase