Faculty Collaboration Database

Extending the cardioprotective window using a novel delta-opioid agonist fentanyl isothiocyanate via the PI3-kinase pathway. Am J Physiol Heart Circ Physiol 2005 Jun;288(6):H2744-9

Date

01/18/2005

Pubmed ID

15653765

DOI

10.1152/ajpheart.00918.2004

Scopus ID

2-s2.0-19344369007 (requires institutional sign-in at Scopus site)   47 Citations

Abstract

Selective delta-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 delta-opioid agonist, fentanyl isothiocyanate (FIT), which binds irreversibly to the delta-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 microg/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 microg/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.

Author List

Gross ER, Peart JN, Hsu AK, Auchampach JA, Gross GJ

Author

John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

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

Analgesics, Opioid
Animals
Blood Pressure
Disease Models, Animal
Fentanyl
Heart Rate
Hemodynamics
Ischemic Preconditioning
Isothiocyanates
Male
Myocardial Infarction
Phosphatidylinositol 3-Kinases
Rats
Rats, Sprague-Dawley
Receptors, Opioid, delta