Extending the cardioprotective window using a novel δ-opioid agonist fentanyl isothiocyanate via the PI3-kinase pathway

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Title Extending the cardioprotective window using a novel δ-opioid agonist fentanyl isothiocyanate via the PI3-kinase pathway
Author Gross, Eric R.; Peart, Jason Nigel John; Hsu, Anna K.; Auchampach, John A.; Gross, Garrett J.
Journal Name American Journal of Physiology: Heart and Circulatory Physiology
Year Published 2005
Place of publication United States
Publisher American Physiological Society
Abstract Selective δ-opioid agonists produce delayed cardioprotection that lasts for 24–48 h in rats; however, the maximum length of the cardioprotective window is unclear. In this study, we attempted to prolong the cardioprotective window using a unique δ-opioid agonist, fentanyl isothiocyanate (FIT), which binds irreversibly to the -receptor, and determined the role of the phosphatidylinositol 3-kinase (PI3K) pathway as a trigger or end effector of FIT-induced cardioprotection. Initially, male rats were administered FIT (10 µg/kg) 10 min before hearts were subjected to 30 min of ischemia and 2 h of reperfusion followed by infarct size (IS) assessment. Acute FIT administration reduced IS when given before ischemia, 5 min before reperfusion, or 10 s after reperfusion compared with control. IS reduction also occurred following a single dose of FIT at 48, 72, 96, and 120 h after administration vs. control, with the maximum effect observed at 96 h. FIT-induced IS reduction at 96 h was completely abolished when the irreversible PI3K inhibitor wortmannin (15 µg/kg) was given before FIT during the trigger phase; however, the effect was only partially abrogated when wortmannin was given 96 h later. These data suggest that FIT has a prolonged cardioprotective window greater than that of any previously described cardioprotective agent that requires PI3K primarily in the trigger phase but also partially, as a mediator or end effector
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1152/ajpheart.00918.2004
Volume 288
Page from H2744
Page to H2749
ISSN 0363-6135
Date Accessioned 2006-07-26
Language en_AU
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Clinical Pharmacology and Therapeutics
URI http://hdl.handle.net/10072/25842
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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