Insights into the cardioprotective function of adenosine A1 and A3 receptors

Vladimir Shneyvays, Liaman K. Mamedova, Dorit Leshem, Avishag Korkus, Asher Shainberg

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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 A1R and A3R against these two different kinds of stress conditions via direct action on isolated cardiomyocytes. Effects of A1 and A3 adenosine receptors were assessed by comparing morphological-functional tolerance, cellular energy state and contribution of the mitochondrial KATP channels during development of hypoxia and DOX cytotoxicity. Methods: The primary cardiac myocyte cultures were treated in a hypoxic chamber of N2 (100%) in glucose-free media. A second group of cells were treated on day 7 in culture with 0.5 to 5 μM DOX for 18 h and then incubated in drug-free growth medium for an additional 24 h or 72 h. The hypoxic and cytotoxic damage was characterized by morphological and biochemical evaluations. Results: The A1R and A3R selective agonists (CCPA and Cl-IB-MECA, respectively) significantly decreased damage to cardiac myocytes under hypoxic conditions. Activation of both A1R and A3R (100 nM) was more efficient in protection against hypoxia than by each one alone. The A3R agonist Cl-IB-MECA (100 nM) shows cardioprotective activity to the DOX-treated cells; however, the A1R agonist CCPA (10 nM to 10 μM) was not effective in protection against DOX toxicity. Conclusion: Activation of both the ADO receptors (A1R and A3R) leads to positive beneficial effects in cultured cardiomyocytes in 90 min hypoxia, but only A3R activation renders positive response against slowly developed DOX toxicity. Hence, the cascade of events involved in cardioprotection appears to be distinct for A1 and A3 receptor signalling.

Original languageEnglish
Pages (from-to)138-145
Number of pages8
JournalExperimental and Clinical Cardiology
Volume7
Issue number2-3
StatePublished - Sep 2002

Keywords

  • Adenosine receptors
  • Cardiomyocytes
  • Cardioprotection
  • Doxorubicin
  • Hypoxia

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