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dc.contributor.authorPeart, Jasonen_US
dc.contributor.authorJ. Gross, Garretten_US
dc.description.abstractA 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 ߭adrenergic receptors (߭AR) in acute and chronic opioid preconditioning. Langendorff-perfused hearts from placebo, acute morphine (AM; 10 孯l/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 ᠴ% baseline; end-diastolic pressure (EDP), 33 ᠳ mmHg], whereas AM hearts showed significant improvement in recovery of RPP and EDP (60 ᠳ% and 23 ᠴ 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 ᠳ%, 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 ߱-AR blockade with CGP-20712A failed to alter recovery in CM hearts, the ߲-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, ߲-AR, and Gs proteins, whereas AM preconditioning is mediated via Gi proteins and PKC.en_US
dc.publisherAmerican Physiological Societyen_US
dc.publisher.placeBethesda MD USAen_US
dc.relation.ispartofjournalAmerican Journal of Physiology - Heart and Circulatory Physiologyen_US
dc.titleCardioprotective effects of acute and chronic opioid treatment are mediated via different signaling pathwaysen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Health, School of Medical Scienceen_US
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.en_US
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