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: Eitaro Kodani, Yu-Ting Xuan, Ken Shinmura, Hitoshi Takano, Xian-Liang Tang, Roberto Bolli
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 283 Issue 5 Pg. H1943-57 (Nov 2002) ISSN: 0363-6135 [Print] United States
• PMID: 12384473 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzamides
• Benzylidene Compounds
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Isoenzymes
• Narcotic Antagonists
• Nitrobenzenes
• Piperazines
• Pyrazoles
• Receptors, Opioid, delta
• Sulfonamides
• N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
• 7-benzylidenenaltrexone
• BW 373U86
• 6-Ketoprostaglandin F1 alpha
• Naltrexone
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• Celecoxib
• Dinoprostone

Topics

• 6-Ketoprostaglandin F1 alpha (analysis)
• Animals
• Benzamides (pharmacology)
• Benzylidene Compounds (pharmacology)
• Celecoxib
• Consciousness
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Dinoprostone (analysis)
• Heart Rate (drug effects)
• Ischemic Preconditioning, Myocardial
• Isoenzymes (antagonists & inhibitors, metabolism)
• Male
• Myocardial Infarction (drug therapy, metabolism)
• Myocardial Stunning (drug therapy, metabolism)
• Myocardium (chemistry, enzymology)
• Naltrexone (analogs & derivatives, pharmacology)
• Narcotic Antagonists (pharmacology)
• Nitrobenzenes (pharmacology)
• Piperazines (pharmacology)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Pyrazoles
• Rabbits
• Receptors, Opioid, delta (metabolism)
• Sulfonamides (pharmacology)