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Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2003 Jul; Vol. 285 (1), pp. H81-9. Date of Electronic Publication: 2003 Mar 13. - Publication Year :
- 2003
-
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.
- Subjects :
- ATP-Binding Cassette Transporters
Adenosine analogs & derivatives
Analgesics, Opioid pharmacology
Animals
Benzylidene Compounds pharmacology
Free Radicals metabolism
In Vitro Techniques
KATP Channels
Mitochondria, Heart physiology
Morphine pharmacology
Myocardial Infarction pathology
Myocardial Reperfusion Injury pathology
Naltrexone pharmacology
Potassium Channels physiology
Potassium Channels, Inwardly Rectifying
Purinergic P1 Receptor Agonists
Purinergic P1 Receptor Antagonists
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species metabolism
Receptors, Opioid, delta antagonists & inhibitors
Receptors, Purinergic P1 physiology
Adenosine pharmacology
Heart Diseases prevention & control
Naltrexone analogs & derivatives
Receptor Cross-Talk drug effects
Receptors, Opioid, delta drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 285
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 12637353
- Full Text :
- https://doi.org/10.1152/ajpheart.00985.2002