Premium
Increased cardiac tolerance to ischemia/reperfusion by delta 2 opioid receptor receptor Deltorphin‐B mediated by NO‐synthase, protein kinase C and tyrosine kinase
Author(s) -
Brown Stephen,
Maslov Leonid N.,
Oeltgen Peter R.
Publication year - 2010
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.24.1_supplement.781.4
Subject(s) - glibenclamide , protein kinase c , pharmacology , chemistry , ischemic preconditioning , medicine , endocrinology , ischemia , kinase , biochemistry , diabetes mellitus
We investigated the contribution of NO‐synthase (NOS), protein kinase C (PKC), tyrosine kinase (TK) and potassium ATP (K ATP ) channel activation to the mechanism(s) of antiarrhythmic action of the selective δ 2 opioid receptor (OR) agonist Deltorphin‐B (Delt‐B). Delt‐B was administered to rats 15 min prior to coronary artery occlusion (45 min) and 10 min reperfusion. Pretreatment with Delt‐B (150 nmol/kg) significantly reduced the incidence of ischemia and reperfusion induced arrhythymias. The NOS inhibitor, L‐NAME, the TK inhibitor, genistein, the PKC inhibitor, chelerythrin, the non‐selective K ATP channel inhibitor, glibenclamide, and the selective mitochondrial K ATP inhibitor 5‐hydroxydecanoate (5‐HD) were also administered prior to coronary artery occlusion. PKC, TK, and NOS inhibitors blocked the arrhythmogenic protection during ischemia/reperfusion provided by peripheral δ 2 activation by Delt‐B. The K ATP blockers glibenclamide and 5‐HD did not abolish the protective effect of Delt‐B. The inhibitors alone were without effect. We conclude that the antiarrhythmic ischemic protection of Delt‐B is mediated in part by mechanism relying on activation of PKC, TK and NOS and does not rely on K ATP channel activation. Supported by a VA Merit Review Grant (SAB), Office of Navel Research (PRO) and the Russian Foundation of Basic Research (LNM).