Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors. Am J Physiol Heart Circ Physiol 2003 Jul;285(1):H81-9
Date
03/15/2003Pubmed ID
12637353DOI
10.1152/ajpheart.00985.2002Scopus ID
2-s2.0-0038339373 (requires institutional sign-in at Scopus site) 83 CitationsAbstract
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.
Author List
Peart JN, Gross GJMESH terms used to index this publication - Major topics in bold
ATP-Binding Cassette TransportersAdenosine
Analgesics, Opioid
Animals
Benzylidene Compounds
Free Radicals
Heart Diseases
In Vitro Techniques
KATP Channels
Mitochondria, Heart
Morphine
Myocardial Infarction
Myocardial Reperfusion Injury
Naltrexone
Potassium Channels
Potassium Channels, Inwardly Rectifying
Purinergic P1 Receptor Agonists
Purinergic P1 Receptor Antagonists
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
Receptor Cross-Talk
Receptors, Opioid, delta
Receptors, Purinergic P1