Medical College of Wisconsin
CTSIResearch InformaticsREDCap

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

03/15/2003

Pubmed ID

12637353

DOI

10.1152/ajpheart.00985.2002

Scopus ID

2-s2.0-0038339373 (requires institutional sign-in at Scopus site)   83 Citations

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.

Author List

Peart JN, Gross GJ



MESH terms used to index this publication - Major topics in bold

ATP-Binding Cassette Transporters
Adenosine
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