title: Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors.
abstract: The relative roles of free-radical production, mitochondrial ATP-sensitive K+ (mitoKATP) channels and possible receptor cross-talk in both opioid and adenosine A1 receptor (A1AR) mediated protection were assessed in a rat model of myocardial infarction. Sprague-Dawley rats were subjected to 30 min of occlusion and 90 min of reperfusion. The untreated rats exhibited an infarct of 58.8 +/- 2.9% [infarct size (IS)/area at risk (AAR), %] at the end of reperfusion. Pretreatment with either the nonselective opioid receptor agonist morphine or the selective A1AR agonist 2-chloro-cyclopentyladenosine (CCPA) dramatically reduced IS/AAR to 41.1 +/- 2.2% and 37.9 +/- 5.5%, respectively (P < 0.05). Protection afforded by either morphine or CCPA was abolished by the reactive oxygen species scavenger N-(2-mercaptopropionyl)glycine or the mitoKATP channel blocker 5-hydroxydecanoate. Both morphine- and CCPA-mediated protection were attenuated by the selective A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine and the selective delta1-opioid receptor (DOR) antagonist 7-benzylidenealtrexone. Simultaneous administration of morphine and CCPA failed to enhance the infarct-sparing effect of either agonist alone. These data suggest that both DOR and A1AR-mediated cardioprotection are mitoKATP and reactive oxygen species dependent. Furthermore, these data suggest that there are converging pathways and/or receptor cross-talk between A1AR- and DOR-mediated cardioprotection.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. jpeart@mcw.edu
authors.forename: Jason N
authors.initials: JN
authors.lastname: Peart
authors.forename: Garrett J
authors.initials: GJ
authors.lastname: Gross
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006331:Heart Diseases / Q000517:prevention & control*; D066298:In Vitro Techniques; D054086:KATP Channels; D008929:Mitochondria, Heart / Q000502:physiology; D009020:Morphine / Q000494:pharmacology; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000187:drug effects*; D018047:Receptors, Purinergic P1 / Q000502:physiology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000701:Analgesics, Opioid; D001597:Benzylidene Compounds; D005609:Free Radicals; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D017382:Reactive Oxygen Species; D017465:Receptors, Opioid, delta; D018047:Receptors, Purinergic P1; C092520:uK-ATP-1 potassium channel; C077358:7-benzylidenenaltrexone; C058394:2-chloro-N(6)cyclopentyladenosine; D009271:Naltrexone; D009020:Morphine; D000241:Adenosine