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

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, beta(1)/beta(2) 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.

Automated summary

Growing evidence suggests that guanine-based purines can modulate smooth muscle contractile activity in blood vessels and the gastrointestinal tract. This study investigated the effects of guanosine and guanine on spontaneous uterine contractions and contractions induced by potassium depolarization and oxytocin in non-pregnant rats. The results showed that guanosine, but not guanine, reduced the amplitude of spontaneous contractions in a dose-dependent manner. Guanosine also inhibited calcium influx-induced contractions and oxytocin-induced contractions. The findings suggest that guanosine has tocolytic effects on the rat myometrium, likely due to its intracellular intake and its effects on extracellular calcium influx and intracellular calcium release.