Delayed cardioprotection is mediated via a non-peptide delta opioid agonist, SNC-121, independent of opioid receptor stimulation. Basic Res Cardiol 2004 Jan;99(1):38-45
Date
12/20/2003Pubmed ID
14685704DOI
10.1007/s00395-003-0438-3Scopus ID
2-s2.0-0347629190 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
Acute cardioprotection is mediated primarily through delta opioid receptor stimulation independent of micro or kappa opioid receptor stimulation. Delayed cardioprotection is mediated by delta opioid receptor agonists but ambiguity remains about direct receptor involvement. Therefore, we investigated the potential of SNC-121, a non-peptide delta opioid agonist, to produce delayed cardioprotection and characterized the role of opioid receptors in this delayed response. All rats underwent 30 minutes of ischemia followed by 2 hours of reperfusion. SNC-121 induced a significant delayed cardioprotective effect. To determine the nature of this SNC-121-induced delayed cardioprotection, rats were treated with specific opioids receptor antagonists and underwent pertussis toxin (PT) treatment prior to opioid agonist stimulation. Control rats were injected with saline and allowed to recover for 24 hours. Pretreatment and early treatment with opioid receptor antagonists failed to inhibit the delayed protective effects of SNC-121, as did pretreatment with PT. Treatment with a free radical scavenger, 2-mercaptopropionyl glycine, at the time of opioid stimulation attenuated the delayed cardioprotective effects of SNC-121. These data suggest that delayed cardioprotection is stimulated via non-peptide delta opioid agonists by a mechanism unrelated to opioid receptor activation. The mechanism appears to be a non-opioid receptor mediated production of reactive oxygen species that triggers the signaling cascade leading to delayed cardioprotection.
Author List
Patel HH, Hsu A, Gross GJMESH terms used to index this publication - Major topics in bold
AnimalsBenzamides
Cardiotonic Agents
Hemodynamics
In Vitro Techniques
Ischemic Preconditioning, Myocardial
Male
Molecular Structure
Myocardial Ischemia
Myocardial Reperfusion
Pertussis Toxin
Piperazines
Rats
Rats, Sprague-Dawley
Receptors, Opioid, delta
Time Factors
Tiopronin
