Home FOR AUTHORS General Physiology and Biophysics 2013 General Physiology and Biophysics Vol.32, No.3, p.325-335, 2013

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General Physiology and Biophysics Vol.32, No.3, p.325-335, 2013

Title: The guinea pig atrial A1 adenosine receptor reserve for the direct negative inotropic effect of adenosine
Author: Zsuzsanna Kiss, Krisztian Pak, Judit Zsuga, Bela Juhasz, Balazs Varga, Andras J. Szentmiklosi, David D. Haines, Arpad Tosaki, Rudolf Gesztelyi
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 A1 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.
Keywords: A1 adenosine receptor — Atrium — Heart — Inotropy — Receptorial responsiveness method
Year: 2013, Volume: 32, Issue: 3 Page From: 325, Page To: 335
doi:10.4149/gpb_2013041


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