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Inhibition of uterine contractility by guanine-based purines in non-pregnant rats

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Growing evidence pointed out that guanine-based purines are able to modulate smooth muscle contractile activity of blood vessels and gastrointestinal tract. Since, so far, possible guanine-based purine modulation of uterine musculature is unknown, the aim of the present study was to investigate in vitro, using organ bath technique, guanosine and guanine effects on spontaneous uterine contraction, and uterine contraction induced by K+-depolarization and oxytocin in a non-pregnant rat. Guanosine, but not guanine, reduced the amplitude of spontaneous contraction of the uterine muscle in a dose-dependent manner. The inhibitory response was antagonized by S-(4-nitrobenzyl)-6-thioinosine (NBTI), a membrane nucleoside transporter inhibitor, but persisted in the presence of theophylline, a nonselective adenosine receptor antagonist, or propanolol, β12 adrenoreceptor antagonist or blockers of a nitrergic pathway. In addition, potassium channel blockers did not influence guanosine-induced effects. Guanosine was able to inhibit the external calcium (Ca2+) influx-induced contraction, but it did not affect the contraction induced by high-KCl solution, indicating that guanosine does not interact with L-type voltage-gated calcium channel. Guanosine prevented/reduced uterine contractions induced by oxytocin, even in the absence of external calcium. In conclusion, guanosine is able to reduce both spontaneous and oxytocin-induced contractions of rat myometrium, likely subsequently to its intracellular intake. The blockade of extracellular Ca2+ influx and reduction of Ca2+ release from the intracellular store are the mechanisms involved in the guanosine-induced tocolytic effects.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


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This study was funded by a grant (FFR 2018) from Ministero dell’Università e della Ricerca Scientifica (MIUR).

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MGZ designed and performed the study, analyzed and interpreted the data, prepared figures, and drafted and edited the manuscript. AC performed the experiments and analyzed the data. RS participated to supervision, experimental design, interpreted the data, and edited and revised the manuscript. All the authors contributed to the critical revision and approved the final version of the manuscript.

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Correspondence to Maria Grazia Zizzo.

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The authors declare no competing interests.

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All animal care was approved by the Animal Care and Use Ethics Committee of the University of Palermo and performed in accordance with national.

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The authors authorize the submission and publication of this article in Naunyn–Schmiedeberg’s Archives of Pharmacology.

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Zizzo, M.G., Cicio, A. & Serio, R. Inhibition of uterine contractility by guanine-based purines in non-pregnant rats. Naunyn-Schmiedeberg's Arch Pharmacol 396, 963–972 (2023).

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