The guinea pig atrial A1 adenosine receptor reserve for the direct negative inotropic effect of adenosine

Zsuzsanna Kiss, Krisztian Pak, Judit Zsuga, Bela Juhasz, Balazs Varga, Andras J. Szentmiklosi, David D. Haines, Arpad Tosaki, Rudolf Gesztelyi

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10 Citations (Scopus)

Abstract

Although the A1 adenosine receptor (A1 receptor), the main adenosine receptor type in cardiac muscle, is involved in powerful cardioprotective processes such as ischemic preconditioning, the atrial A 1 receptor reserve has not yet been quantified for the direct negative inotropic effect of adenosine. In the present study, adenosine concentration-effect (E/c) curves were constructed before and after pretreatment with FSCPX (8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)benzoyloxy) propyl]- N1-propylxanthine), an irreversible A1 receptor antagonist, in isolated guinea pig atria. To prevent the intracellular elimination of the administered adenosine, NBTI (S-(2-hydroxy-5-nitrobenzyl)-6- thioinosine), a nucleoside transport inhibitor, was used. As expected, NBTI alone and FSCPX-pretreatment alone shifted the adenosine E/c curve to the left and right, respectively. However, in the presence of NBTI, FSCPX-pretreatment appeared to increase the maximal response to adenosine. By means of the receptorial responsiveness method (RRM), our recently developed procedure, adenosine E/c curves generated in the presence of NBTI were corrected for the bias caused by the endogenous adenosine accumulated by NBTI. The corrected curves indicate a substantial A1 receptor reserve for the direct negative inotropy evoked by adenosine. In addition, our results suggest that accumulation of an endogenous agonist may bias the E/c curve constructed with the same or similar agonist that can lead to seemingly paradoxical results.

Original languageEnglish
Pages (from-to)325-335
Number of pages11
JournalGeneral physiology and biophysics
Volume32
Issue number3
DOIs
Publication statusPublished - Sep 13 2013

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Keywords

  • A adenosine receptor
  • Atrium
  • Heart
  • Inotropy
  • Receptorial responsiveness method

ASJC Scopus subject areas

  • Biophysics
  • Physiology

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