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OBJECTIVE: The aim of this study was to investigate the effects of melatonin on spontaneous and oxytocin-induced contractility of pregnant and non-pregnant rat myometrium in vitro. DESIGN: Myometrial strips were removed from virgin or late pregnant (21 days gestation) Wistar rats following decapitation and placed in an organ bath containing Krebs’ solution at 37°C and pH 7.4, constantly bubbled with 95% oxygen-5% carbon dioxide and isometric contractions were recorded. Effects of cumulative concentrations of melatonin (0.1 to 10 μM) on spontaneous and oxytocin-induced contractions were studied. Possible involvement of Ca2+-activated K+ channels in inhibitory actions of melatonin was investigated by using apamin (100 nM). RESULTS: Melatonin inhibited spontaneous and oxytocin-induced contractions of myometrium from both virgin and late pregnant rats in a dosedependent manner. After inhibition of oxytocin-induced contractions by melatonin, application of prostaglandin F2α (1 μM) but not high KCl (30mM) containing solution initiated contractile activity. Inhibitory response induced by melatonin (13μM) was not affected by apamin (100 nM). CONCLUSIONS: Data from this study demonstrates that melatonin inhibits spontaneous and oxytocin-induced contractions of myometrium from pregnant and non-pregnant rats. Although the exact mechanism is not clear, melatonin-induced inhibition of myometrial contractions may results from its interactions with Ca2+ channels. A portion of this work has been previously presented in an abstract form (Physiological Society Meeting, The Journal of Physiology 528 P, Aberdeen, 2000)