Home General Physiology and Biophysics 2024 General Physiology and Biophysics Vol.43, No.6, p, 577–584, 2024

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General Physiology and Biophysics Vol.43, No.6, p, 577–584, 2024

Title: The ex vivo effects of hypoxanthine-tricyclano, a synthetic adenosine analogue, on rat left and right atria
Author: Ignac Ovari, Gabor Viczjan, Miklos Bege, Aniko Borbas, Pal Herczegh, Judit Zsuga, Zoltan Papp, Zoltan Szilvassy, Bela Juhasz, Rudolf Gesztelyi, Tamas Erdei
Abstract: Hypoxanthine-tricyclano is a synthetic adenosine analogue, in which adenine and ribose have been replaced by hypoxanthine and a morpholino-derived tricyclic moiety, respectively. We investigated whether hypoxanthine-tricyclano could influence atrial inotropy and/or chronotropy, two important functions regulated by the A1 receptor, the main adenosine receptor type of the supraventricular myocardium. Paced left atria and spontaneously beating right atria, isolated from male, 30–35 weeks old, Wistar rats, were used. The ino- and chronotropic effects of adenosine and hypoxanthine-tricyclano (separately and together) were assessed in the absence and presence of 8-cyclopentyl-1,3-dipropylxanthine (CPX), a selective, orthosteric, reversible A1 adenosine receptor antagonist. We found that adenosine exerted a strong negative inotropic effect (similar in left and right atria). However, hypoxanthine-tricyclano elicited a moderate positive inotropic effect (also similar in all atria). In right atria, adenosine evoked a robust negative chronotropic effect, whereas hypoxanthine-tricyclano produced a slight positive chronotropy. CPX blunted the effects of both adenosine and hypoxanthine-tricyclano, although this antagonism was strong (and significant) for adenosine, while smaller (and non-significant) for hypoxanthine-tricyclano. Both effects of hypoxanthine-tricyclano were easily surmountable with adenosine. Thus, hypoxanthine-tricyclano may act as a week, orthosteric, reversible, inverse and low-affinity agonist of the A1 receptor, although alternative mechanisms of action cannot be excluded.
Keywords: Adenosine — Hypoxanthine-tricyclano — Rat — Atrium (ex vivo) — A1 adenosine receptor — Inotropic effect — Chronotropic effect
Published online: 14-Nov-2024
Year: 2024, Volume: 43, Issue: 6 Page From: 577, Page To: 584
doi:10.4149/gpb_2024033


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