TY - JOUR T1 - Cardioprotection of Interleukin-2 Is Mediated via κ-Opioid Receptors JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 560 LP - 567 DO - 10.1124/jpet.103.061135 VL - 309 IS - 2 AU - Chun-Mei Cao AU - Qiang Xia AU - Jie Tu AU - Mai Chen AU - Song Wu AU - Tak-Ming Wong Y1 - 2004/05/01 UR - http://jpet.aspetjournals.org/content/309/2/560.abstract N2 - We examined whether interleukin-2 (IL-2) protects the myocardium against injury induced by ischemia and reperfusion via the κ-opioid receptor (OR). The cardioprotective effect of IL-2 was evaluated by measuring infarct size and lactate dehydrogenase (LDH) release in response to ischemia and reperfusion in the isolated rat heart. IL-2 at an optimal dose of 50 U/ml mimicked the effect of ischemic preconditioning by reducing infarct size and LDH release. The infarct and LDH-reducing effects of IL-2 were blocked by nor-binaltorphimine (5 μM), a κ-OR antagonist, but not naltrindole (5 μM), a δ-OR antagonist known to block the action of its stimulation. Moreover, blockade of the mitochondrial ATP-sensitive potassium (mito-KATP) channel with a selective antagonist, 5-hydroxydecanoate (100 μM), or a nonselective antagonist of KATP channels, glybenclamide (100 μM), or blockade of protein kinase C (PKC) with its inhibitors chelerythrine (5 μM) or GF 109203X (10 μM) [3-[1-[3-(dimethylaminopropyl]-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione monohydrochloride] abolished the protective effect of IL-2. Administration of free radical scavengers N-acetylcysteine (4 mM) or N-(2-mercaptopropionyl)-glycine (1 mM) also abolished the protective effects of IL-2 and U50,488H [(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide], a selective κ-OR agonist. This study provides the first evidence that IL-2 confers cardioprotection against injury induced by ischemia/reperfusion. The effect of IL-2 is mediated via κ-OR as evidenced by κ-OR antagonism and similar signaling mechanisms, mito-KATP, PKC, and reactive oxygen species involved in the cardioprotective effects of both IL-2 and κ-OR stimulation. The American Society for Pharmacology and Experimental Therapeutics ER -