{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:42:07Z","timestamp":1791164527436,"version":"4.1.0"},"reference-count":34,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:p> Morphine has cardioprotective effects against ischemic-reperfusion injuries. This study investigates whether morphine could mimic the antiapoptotic effect of preconditioning using a model of cultured neonatal rat cardiomyocytes subjected to metabolic inhibition (MI). To quantify MI-induced apoptosis, DNA fragmentation and mitochondrial cytochrome c release levels were measured by ELISA. MI-dependent DNA fragmentation was prevented by both Z-VAD-fmk (20 \u03bcM), a pan-caspase inhibitor, and cyclosporine A (CsA; 5 \u03bcM), a mitochondrial pore transition blocker, added during MI (36% and 54% decrease, respectively). MI-dependent cytochrome c release was not blocked by Z-VAD-fmk but was decreased (38%) by CsA during MI. Metabolic preconditioning (MIP) and preconditioning with morphine (1 \u03bcM) were also assessed. MI-dependent DNA fragmentation and cytochrome c release were prevented by MIP (40% and 45% decrease, respectively) and morphine (34% and 45%, respectively). The antiapoptotic effect of morphine was abolished by naloxone (10 nM), a nonselective opioid receptor antagonist, or xestospongin C (XeC, 400 nM), an inhibitor of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P<jats:sub>3<\/jats:sub>]-mediated Ca<jats:sup>2+<\/jats:sup> release. Ca<jats:sup>2+<\/jats:sup> preconditioning, induced by increasing extracellular Ca<jats:sup>2+<\/jats:sup> from 1.8 to 3.3 mM, mimicked the antiapoptotic effect of morphine on DNA fragmentation (24% decrease) and cytochrome c release (57% decrease). This effect mediated by extracellular Ca<jats:sup>2+<\/jats:sup> was also abolished by XeC. Measurements of intracellular Ca<jats:sup>2+<\/jats:sup> concentration using fura-2 microspectrofluorimetry showed that morphine induces Ins(1,4,5)P<jats:sub>3<\/jats:sub>-dependent Ca<jats:sup>2+<\/jats:sup> transients abolished by 2-aminoethoxydiphenyl borate (2-APB), a cell-permeable Ins(1,4,5)P<jats:sub>3<\/jats:sub> antagonist. These results suggest that morphine preconditioning prevents simulated ischemia-reperfusion-induced apoptosis via an Ins(1,4,5)P<jats:sub>3<\/jats:sub> signaling pathway in rat ventricular myocytes. <\/jats:p>","DOI":"10.1152\/ajpheart.00881.2003","type":"journal-article","created":{"date-parts":[[2004,9,2]],"date-time":"2004-09-02T20:25:10Z","timestamp":1094156710000},"page":"H83-H88","source":"Crossref","is-referenced-by-count":27,"title":["Morphine mimics the antiapoptotic effect of preconditioning via an Ins(1,4,5)P<sub>3<\/sub> signaling pathway in rat ventricular 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