Abstract | BACKGROUND:
Opioid preconditioning protects the myocardium against ischemia/reperfusion (IR) injury. By enhancing cardiomyocyte viability, opioids can enhance cardiac function and recovery from IR injury during acute cardiac care. The myocyte model HL-1 is an immortalized, mouse atrial cell line that expresses functional delta-opioid receptors. The HL-1 myocyte may be useful for IR injury research exploring opioid cardioprotection. MATERIALS AND METHODS: RESULTS: Compared to untreated control, the LDH assay showed significant reduction in opioid-only pretreated groups at all time points. These effects were attenuated with delta- opioid antagonist co-administration. Co-administration of non-selective K( ATP) channel closer glybenclamide and DADLE abolished DADLE cytoprotection, while selective mitochondrial K( ATP) opener diazoxide mimicked DADLE cytoprotection Co-administration of chelerythrine and DADLE significantly reduced chelerythrine cytotoxicity. CONCLUSION: Delta- opioid preconditioning of HL-1 myocytes significantly decreased necrosis from in vitro simulated ischemia/reperfusion as measured by LDH release; this effect was reversed by delta-antagonist naltrindole. Cytoprotection was PKC and K( ATP) channel-dependent. HL-1 myocytes exhibit opioid-induced cytoprotection from IR injury, and present a novel model of pharmacologic preconditioning.
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Authors | Elisabeth M Seymour, Shu-Yung James Wu, Melissa A Kovach, Matthew A Romano, Jonathan R Traynor, William C Claycomb, Steven F Bolling |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 114
Issue 2
Pg. 187-94
(Oct 2003)
ISSN: 0022-4804 [Print] United States |
PMID | 14559445
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Alkaloids
- Benzophenanthridines
- Enzyme Inhibitors
- Membrane Proteins
- Phenanthridines
- Potassium Channels
- Receptors, Opioid, delta
- mitochondrial K(ATP) channel
- Naltrexone
- Enkephalin, Leucine-2-Alanine
- chelerythrine
- Protein Kinase C
- naltrindole
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Topics |
- Alkaloids
- Animals
- Benzophenanthridines
- Cell Line
- Enkephalin, Leucine-2-Alanine
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Heart
(drug effects, physiology)
- Ischemic Preconditioning, Myocardial
(methods)
- Kinetics
- Membrane Proteins
(drug effects, physiology)
- Muscle Cells
(physiology)
- Myocardial Reperfusion
- Myocardium
(cytology)
- Naltrexone
(analogs & derivatives, pharmacology)
- Phenanthridines
(pharmacology)
- Potassium Channels
- Protein Kinase C
(antagonists & inhibitors, metabolism)
- Receptors, Opioid, delta
(drug effects, physiology)
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