Prolonged morphine administration alters protein expression in the rat myocardium

Morphine was administered to adult male Wistar rats in high doses (10 mg/kg per day) for 10 days. Proteins from the plasma membrane- and mitochondria-enriched fractions or cytosolic proteins isolated from left ventricles were run on 2D gel electrophoresis, scanned and quantified with specific software to reveal differentially expressed proteins.Nine proteins were found to show markedly altered expression levels in samples from morphine-treaded rats and these proteins were identified by mass spectrometric analysis. They belong to different cell pathways including signaling, cytoprotective, and structural elements.The present identification of several important myocardial proteins altered by prolonged morphine treatment points to global effects of this drug on heart tissue. These findings represent an initial step toward a more complex view on the action of morphine on the heart.Morphine, a highly effective analgesic used for treatment of different kinds of chronic pain states, may also exert significant cardiovascular effects [1-3]. Moreover, under certain conditions, this drug can be also implicated in the acquisition of cardioprotection against ischaemia-reperfusion injury [4-6]. However, the molecular mechanisms and consequences of morphine actions on the heart have not yet been fully elucidated. The majority of studies dealing with morphine in the field of cardiology are oriented on clinical usage of this drug and current cardiovascular research has been limited to the evaluation of factors or pathways believed to contribute to its physiological action, such as δ- and κ-opioid receptors, cyclooxygenase-2, inducible nitric oxide synthase or reactive oxygen species [7-10]. Because of great importance of this drug in clinical practice, and in view of morphine unwanted effects on one side and cardioprotective potential on the other, investigation of its impact on the heart at the molecular level deserves more attention. A better understanding of the molecular mechani