Cardioprotective effects of acute and chronic opioid treatment are mediated via different signaling pathways

There are no files associated with this record.

Title Cardioprotective effects of acute and chronic opioid treatment are mediated via different signaling pathways
Author Peart, Jason Nigel John; Gross, Garrett J.
Journal Name American Journal of Physiology - Heart and Circulatory Physiology
Year Published 2006
Place of publication Bethesda MD USA
Publisher American Physiological Society
Abstract A 5-day exposure to morphine exerts a profound cardioprotective phenotype in murine hearts. In the present study, we examined mechanisms by which morphine generates this effect, exploring the roles of Gi and Gs proteins, PKA, PKC, and β-adrenergic receptors (β-AR) in acute and chronic opioid preconditioning. Langendorff-perfused hearts from placebo, acute morphine (AM; 10 µmol/l)-, or chronic morphine (CM)-treated mice (75-mg pellet, 5 days) underwent 25-min ischemia and 45-min reperfusion. After reperfusion, placebo-treated hearts exhibited marked contractile and diastolic dysfunction [rate-pressure product (RPP), 40 ± 4% baseline; end-diastolic pressure (EDP), 33 ± 3 mmHg], whereas AM hearts showed significant improvement in recovery of RPP and EDP (60 ± 3% and 23 ± 4 mmHg, respectively; P < 0.05 vs. placebo). Furthermore, CM hearts demonstrated a complete return of diastolic function and significantly greater recovery of contractile function (83 ± 3%, P < 0.05 vs. both placebo and AM). Pretreatment with Gi protein inhibitor pertussis toxin abolished AM protection while partially attenuating CM recovery (P < 0.05 vs. placebo). Treatment with Gs inhibitor NF-449 did not affect AM preconditioning yet completely abrogated CM preconditioning. Similarly, PKA inhibition significantly attenuated the ischemia-tolerant state afforded by CM, whereas it was ineffective in AM hearts. PKC inhibition with chelerythrine was ineffective in CM hearts while completely abrogating AM preconditioning. Moreover, whereas β1-AR blockade with CGP-20712A failed to alter recovery in CM hearts, the β2-AR antagonist ICI-118,551 significantly attenuated postischemic recovery. These data describe novel findings whereby CM preconditioning is mediated by a PKC-independent pathway involving PKA, β2-AR, and Gs proteins, whereas AM preconditioning is mediated via Gi proteins and PKC.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1152/ajpheart.00233.2006
Volume 291
Issue Number 4
Page from H1746
Page to H1753
ISSN 0363-6135
Date Accessioned 2006-06-30
Date Available 2009-09-28T06:51:58Z
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/10072/25841
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1a

Brief Record

Griffith University copyright notice