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This Article Full Text Full Text (PDF) All Versions of this Article: 285/3/H1032    most recent 01004.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Cao, Z. Articles by Van Winkle, D. M. Search for Related Content PubMed PubMed Citation Articles by Cao, Z. Articles by Van Winkle, D. M.

Activation of - and -opioid receptors by opioid peptides protects cardiomyocytes via K_ATP channels

¹Research and Anesthesiology Services, Veterans Affairs Medical Center; and ²Department of Anesthesiology, Oregon Health Sciences University, Portland, Oregon 97201

Submitted 21 November 2002 ; accepted in final form 29 April 2003

To examine the receptor specificity and the mechanism of opioid peptide-induced protection, we examined freshly isolated adult rabbit cardiomyocytes subjected to simulated ischemia. Cell death as a function of time was assessed by trypan blue permeability. Dynorphin B (DynB) and Met⁵-enkephalin (ME) limitation of cell death (expressed as area under the curve) was sensitive to blockade by naltrindole (NTI, a -selective antagonist) and 5'-guanidinyl-17-(cyclopropylmethyl)-6,7-dehydro-4,5-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan (GNTI dihydrochloride, a -selective antagonist): 85.7 ± 2.7 and 142.9 ± 2.7 with DynB and DynB + NTI, respectively (P < 0.001), 94.1 ± 4.2 and 164.5 ± 7.3 with DynB and DynB + GNTI, respectively (P < 0.001), 111.9 ± 7.0 and 192.1 ± 6.4 with ME and ME + NTI, respectively (P < 0.001), and 120.2 ± 4.3 and 170.0 ± 3.3 with ME and ME + GNTI, respectively (P < 0.001). Blockade of ATP-sensitive K⁺ channels eliminated DynB- and ME-induced protection: 189.6 ± 5.4 and 139.0 ± 5.4 for control and ME, respectively (P < 0.001), and 210 ± 5.9 and 195 ± 6.1 for 5-HD and ME + 5-HD, respectively (P < 0.001); 136.0 ± 5.7 and 63.4 ± 5.4 for control and ME, respectively (P < 0.001), and 144.6 ± 4.5 and 114.6 ± 7.7 for HMR-1098 and ME + HMR-1098, respectively (P < 0.01); 189.6 ± 5.4 and 139.0 ± 5.4 for control and ME, respectively (P < 0.001), and 210 ± 5.9 and 195 ± 6.1 for 5-HD and ME + 5-HD, respectively (P < 0.001); and 136.0 ± 5.7 and 63.4 ± 5.4 for control and ME, respectively (P < 0.001), and 144.6 ± 4.5 and 114.6 ± 7.7 for HMR-1098 and ME + HMR-1098, respectively (P < 0.01). We conclude that opioid peptide-induced cardioprotection is mediated by - and -receptors and involves sarcolemmal and mitochondrial ATP-sensitive K⁺ channels.

heart; ischemic preconditioning; hypoxia

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