Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors

• Published in: American journal of physiology. Heart and circulatory physiology 2003-07, Vol.285 (1), p.H81-H89
• Main Authors: Peart, Jason N, Gross, Garrett J
• Format: Article
• Language: English
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Analgesics, Opioid - pharmacology; Animals; ATP-Binding Cassette Transporters; Benzylidene Compounds - pharmacology; Free Radicals - metabolism; Heart Diseases - prevention & control; In Vitro Techniques; KATP Channels; Mitochondria, Heart - physiology; Morphine - pharmacology; Myocardial Infarction - pathology; Myocardial Reperfusion Injury - pathology; Naltrexone - analogs & derivatives; 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; Receptor Cross-Talk - drug effects; Receptors, Opioid, delta - antagonists & inhibitors; Receptors, Opioid, delta - drug effects; Receptors, Purinergic P1 - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00985.2002

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 Submitted 4 December 2002 ; accepted in final form 3 February 2003 The relative roles of free-radical production, mitochondrial ATP-sensitive K + (mitoK ATP ) channels and possible receptor cross-talk in both opioid and adenosine A 1 receptor (A 1 AR) 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 A 1 AR 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 mitoK ATP channel blocker 5-hydroxydecanoate. Both morphine- and CCPA-mediated protection were attenuated by the selective A 1 AR antagonist 1,3-dipropyl-8-cyclopentylxanthine and the selective 1 -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 A 1 AR-mediated cardioprotection are mitoK ATP and reactive oxygen species dependent. Furthermore, these data suggest that there are converging pathways and/or receptor cross-talk between A 1 AR- and DOR-mediated cardioprotection. reactive oxygen species; ATP-sensitive potassium channel Address for reprint requests and other correspondence: G. J. Gross, Dept. of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226 (E-mail: jpeart{at}mcw.edu ).