Korean J Anesthesiol.  2011 May;60(5):351-356. 10.4097/kjae.2011.60.5.351.

Kappa-opioid receptor activation during reperfusion limits myocardial infarction via ERK1/2 activation in isolated rat hearts

• Kim JH
• Jang YH
• Chun KJ
• Kim J
• Park YH
• Kim JS
• Kim JM
• Lee MY

• KMID: 1780180
• DOI: http://doi.org/10.4097/kjae.2011.60.5.351

Abstract

BACKGROUND
We investigated whether p42/p44 extracellular signal-regulated kinases (ERK1/2) and/or phosphatidylinositol-3-OH kinase (PI3K)-Akt play a crucial role in cardioprotection by kappa-opioid receptor (KOP) activation.
METHODS
Langendorff perfused rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Antagonists of ERK1/2 and PI3K were perfused in hearts treated with the KOP agonist U50488H (U50). Infarct size was measured after 2 h of reperfusion. The phosphorylation states of ERK1/2 and Akt by Western immunoblots were determined. Drugs were perfused for a period of 5 min before and 30 min after reperfusion.
RESULTS
Inhibition of ERK1/2 (26.8 +/- 2.9%, P < 0.05 vs. U50) but not PI3K (15.5 +/- 1.1%, P > 0.05 vs. U50) completely abrogated the anti-infarct effect of U50488H. Western blot analysis revealed a significant increase in ERK1/2 but not Akt phsophorylation in U50488H-treated hearts as compared to control hearts when measured immediately after reperfusion.
CONCLUSIONS
KOP activation effectively reduces myocardial infarction. The anti-infarct effect of U50488H is mediated by the ERK1/2, but not the PI3K-Akt pathway.

Keyword

Coronary occlusion; Heart; Myocardial function; Opioid receptors; Reperfusion

MeSH Terms

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
Animals
Blotting, Western
Coronary Occlusion
Extracellular Signal-Regulated MAP Kinases
Heart
Ischemia
Myocardial Infarction
Phosphatidylinositol 3-Kinases
Phosphorylation
Rats
Receptors, Opioid
Reperfusion
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
Extracellular Signal-Regulated MAP Kinases
Phosphatidylinositol 3-Kinases
Receptors, Opioid