title: Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts.
abstract: OBJECTIVE
  Our previous studies demonstrated that remote electro-stimulation (RES) increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R) injury in rat hearts. However, the role of various opioid receptors (OR) subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart.
  
  
  RESULTS
  Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR) subtype receptors (KOR, DOR, and MOR). The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.
  
  
  CONCLUSIONS
  The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Hsin-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.affiliation: Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Shiang-Suo
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan, ROC.
authors.forename: Meng-Ting
authors.initials: MT
authors.lastname: Tsou
authors.affiliation: Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Hsiao-Ting
authors.initials: HT
authors.lastname: Wang
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Division of General Surgery, Department of Surgery, Cheng-Hsin General Hospital, Taipei, Taiwan, ROC.
authors.forename: Jen-Hwey
authors.initials: JH
authors.lastname: Chiu
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D019194:Ischemic Preconditioning; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D011957:Receptors, Opioid / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D011957:Receptors, Opioid; D051057:Proto-Oncogene Proteins c-akt