Insights into the cardioprotective function of adenosine A(1) and A(3) receptors.

Objectives: Cardioprotection (delaying of irreversible damage in hypoxia or prevention of doxorubicin [DOX] toxicity) is achieved by increasing the energy supply, or decreasing the energy demand in the cell and may be regulated through adenosine (ADO) receptor (AR) signalling. The aim of this study was to define of the protective role of ADO A(1)R and A(3)R against these two different kinds of stress conditions via direct action on isolated cardiomyocytes. Effects of A(1) and A(3) adenosine receptors were assessed by comparing morphological-functional tolerance, cellular energy state and contribution of the mitochondrial K(ATP) channels during development of hypoxia and DOX cytotoxicity.

Cardiomyocyte resistance to doxorubicin mediated by A(3) adenosine receptor.

Recently, we reported that the activation of A(3) adenosine receptor (A(3)R) in newborn cultured cardiomyocytes by highly selective agonist Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide) induces protection against the anthracycline antibiotic doxorubicin (DOX) cardiotoxicity. The present study was undertaken to further characterize the cardioprotective action of A(3)R activation by revealing the structural changes in cardiomyocytes elicited upon exposure to DOX. Morphological observations (ultrastructural and immunocytochemical) indicate that after DOX treatment, the cardiomyocytes undergo destructive alterations, and protective action of A(3)R is not connected with its anti-apoptotic activity.