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Activation of peripheral delta‐2 opioid receptors increases tolerance to ischemia/reperfusion injury
Author(s) -
Oeltgen Peter R.,
Maslov Leonid N.,
Brown Stephen A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.793.10
Subject(s) - chelerythrine , naltrindole , cardioprotection , glibenclamide , chemistry , protein kinase c , pharmacology , endocrinology , opioid receptor , medicine , guanethidine , potassium channel , atp sensitive potassium channel , stimulation , receptor , opioid , ischemia , biochemistry , signal transduction , diabetes mellitus
We investigated the role of peripheral δ 2 opioid receptors (OR) in cardiac tolerance to ischemia/reperfusion injury and examined the contribution of Protein Kinase C (PKC), tyrosine kinase (TK), potassium ATP (K ATP ) channels and the autonomic nervous system in δ 2 cardioprotection. Deltorphin II and inhibitors were administered prior to coronary artery occlusion and reperfusion in a rat model. Rats were monitored for the development of arrhythmias and infarct development. Pretreatment with δ 2 specific OR antagonist naltriben completely abolished the cardioprotective effects of Deltorphin II. In contrast the selective δ 1 OR antagonist 7‐Benzylidenenaltrexone had no effect. The PKC inhibitor chelerythrine and the nitric oxide synthase (NOS) inhibitor L‐NAME (N‐nitro‐L‐arginine methyl ester) also reversed both Deltorphin II effects. The nonselective K ATP channel inhibitor glibenclamide and the selective mitochondrial K ATP channel inhibitor 5‐hydroxydecanoic acid abolished the infarct‐sparing effect of Deltorphin II. Inhibition of TK with genistein, the ganglion blocker hexamethonium and the depletion of endogenous catecholamine storage with guanethidine reversed the antiarrhythmic action of deltorphin II, but did not change its infarct sparing action. The cardioprotective mechanism of Deltorphin II is mediated via stimulation of peripheral δ 2 opioid receptors.