Special sensitization pattern in adenosine-induced myocardial responses after thyroxine-treatment

Rudolf Gesztelyi, Judit Zsuga, Ágnes Cseppentõ, Ágnes Bajza, Angelika Varga, Judit Zs Szabó, A. József Szentmiklósi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Chronic thyroxine treatment reduces the susceptibility of atrial myocardium to adenosine. While the possible role of membrane adenosine receptors in this action is supported by several studies, the involvement of intracellular adenosine mechanisms has not been defined. The present experiments were carried out in electrically driven euthyroid and hyperthyroid guinea pig atrial myocardium. The extracellular and intracellular actions of adenosine were analyzed pharmacologically by the use of specific blockers of membrane adenosine transport and intracellular adenosine deaminase (ADA). The involvement of phosphoprotein phosphatase, phospholamban, and sarcoplasmic reticulum Ca2+ ATPase (SERCA) in the adenosine-induced responses was also studied. The major findings were as follows: i) pD2- and Emax-values for adenosine-induced decrease of mechanical activity were significantly reduced after an 8-day thyroxine treatment in atrial tissues; ii) in atria of thyroxine-treated animalsj membrane purine transport inhibitors (dipyridamole, NBTI) induced similar leftward shifts in concentration-response curves for adenosine in both euthyroid and hyperthyroid atrial myocardium without altering the depressed Emax values; iii) the leftward displacement evoked by inhibitors of intracellularly located ADA (coformycin, EHNA) was more striking in hyperthyroid than euthyroid myocardia. ADA inhibitors induced a complete reversal of the maximum adenosine actions; iv) inhibition by cantharidin of phosphoprotein phosphatases (after inhibition of ADA) reduced the adenosine-induced responses. This inhibition was stronger in hyperthyroid atria; v) pharmacological elimination of sarcoplasmic reticulum Ca2+ ATPase by cyclopiazonic acid did not alter the cardiac responses to adenosine and this was independent of thyroid status. It is suggested that distinct modulation of the extra- and intracellular adenosine actions is present in eu- and hyperthyroid hearts. In the latter, a predominance of intracellular adenosine mechanisms can be proposed.

Original languageEnglish
Pages (from-to)295-304
Number of pages10
JournalJournal Pharmacological Sciences
Volume91
Issue number4
DOIs
Publication statusPublished - Apr 1 2003

Keywords

  • Adenosine
  • Adenosine deaminase
  • Myocardium
  • Phosphoprotein phosphatase
  • Thyroxine

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Special sensitization pattern in adenosine-induced myocardial responses after thyroxine-treatment'. Together they form a unique fingerprint.

  • Cite this