title: Delta-opioid receptor-induced late preconditioning is mediated by cyclooxygenase-2 in conscious rabbits.
abstract: Although activation of delta-opioid receptors is known to induce both early and late preconditioning (PC) against myocardial infarction, the mechanisms for this salubrious effect are unclear. Furthermore, it is unknown whether delta-opioid receptors can also induce late PC against myocardial stunning. By using conscious rabbits (n = 120) in this study, we found that the delta-opioid receptor agonist (+/-)-4-[(alpha-R*)-alpha-[(2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-hydroxybenzyl]-N,N-diethylbenzamide (BW-373U86) induced late PC against myocardial stunning 24 h after treatment and that this effect was abolished by the selective cyclooxygenase-2 (COX-2) inhibitors N-[2-(cyclohexyloxy)4-nitrophenyl]methanesulfonamide (NS-398) and celecoxib. This protective effect was also abrogated by the selective delta(1)-opioid receptor antagonist 7-benzylidenenaltrexone, indicating that the delta(1)-opioid receptor is necessary for BW-373U86-induced late PC. BW-373U86 did not induce early PC against stunning. In addition, BW-373U86 induced late PC against infarction, which was blocked by NS-398. At 24 h after BW-373U86 administration, myocardial COX-2 protein expression and PGE(2) and 6-keto-PGF(1alpha) levels were significantly increased. These results demonstrate that activation of delta-opioid receptors induces late PC against both stunning and infarction via a COX-2-dependent mechanism.
authors.affiliation: Experimental Research Laboratory, Division of Cardiology, University of Louisville and Jewish Heart and Lung Institute, Louisville, KY 40292, USA.
authors.forename: Eitaro
authors.initials: E
authors.lastname: Kodani
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Xuan
authors.forename: Ken
authors.initials: K
authors.lastname: Shinmura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takano
authors.forename: Xian-Liang
authors.initials: XL
authors.lastname: Tang
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000494:pharmacology; D000068579:Celecoxib; D003243:Consciousness; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis; D006339:Heart Rate / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism; D017682:Myocardial Stunning / Q000188:drug therapy / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles; D011817:Rabbits; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D001549:Benzamides; D001597:Benzylidene Compounds; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009292:Narcotic Antagonists; D009578:Nitrobenzenes; D010879:Piperazines; D011720:Pyrazoles; D017465:Receptors, Opioid, delta; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C077358:7-benzylidenenaltrexone; C083877:BW 373U86; D015121:6-Ketoprostaglandin F1 alpha; D009271:Naltrexone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D015232:Dinoprostone