Adenosine deaminase inhibition enhances the inotropic response mediated by A1 adenosine receptor in hyperthyroid guinea pig atrium

Adam Kemeny-Beke, Anita Jakab, Judit Zsuga, Miklos Vecsernyes, Denes Karsai, Fanni Pasztor, Maria Grenczer, Andras Jozsef Szentmiklosi, Andras Berta, Rudolf Gesztelyi

Research output: Article

9 Citations (Scopus)

Abstract

The aim of the present study was to test the hypothesis that inhibition of adenosine deaminase (ADA) enhances the efficiency of signal-transduction of myocardial A1 adenosine receptors in hyperthyroidism. The inotropic response to N6-cyclopentyladenosine (CPA), a selective A1 adenosine receptor agonist resistant to ADA, was investigated in the absence or presence of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an ADA and cGMP-stimulated 3′,5′-cyclic nucleotide phosphodiesterase (PDE2) inhibitor, or of pentostatin (2′-deoxycoformycin; DCF), an exclusive ADA inhibitor, in left atria isolated from eu- or hyperthyroid guinea pigs. Both ADA inhibitors enhanced the effect of CPA only in hyperthyroid atria. EHNA significantly increased the Emax (mean ± S.E.M.) from 83.8 ± 1.2% to 93.4 ± 1.2%, while DCF significantly decreased the log EC50 from -7.5 ± 0.07 to -7.83 ± 0.07 in hyperthyroid samples. Conversely, EHNA also diminished the log EC50 (from -7.5 ± 0.07 to -7.65 ± 0.07) and DCF also raised the Emax (from 83.8 ± 1.2% to 85.7 ± 2%) in hyperthyroidism, but these changes were not significant. In conclusion, ADA inhibition moderately but significantly enhanced the efficiency of A1 adenosine receptor signaling pathway in the hyperthyroid guinea pig atrium. This suggests that elevated intracellular adenosine level caused by ADA inhibition may improve the suppressed responsiveness to A1 adenosine receptor agonists associated with the hyperthyroid state. Alternatively or in addition, the role of decreased concentration of adenosine degradation products cannot be excluded. Furthermore, in the case of EHNA, inhibition of PDE2 also appears to contribute to the enhanced A1 adenosine receptor signaling in the hyperthyroid guinea pig atrium.

Original languageEnglish
Pages (from-to)124-131
Number of pages8
JournalPharmacological Research
Volume56
Issue number2
DOIs
Publication statusPublished - aug. 1 2007

ASJC Scopus subject areas

  • Pharmacology

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