The study was conducted to examine effects of a selective copper(l) chelator, neocuproine on the spontaneous or oxytocin-induced contractions in isolated ovariectomized non-pregnant rat, pregnant rat and pregnant human uterus. Uterus activity was evaluated in tissues obtained from bilaterally ovariectomized non-pregnant rats on the 21st day of the operation (n = 24), pregnant rats on the 19-21 st day of gestation (n=24) and women undergoing caesarean section at 38-42 weeks of pregnancy (n=15). Neocuproine (100 mu M) significantly suppressed the amplitude and frequency of the spontaneous contractions in the ovariectomized non-pregnant rat uterus while this agent facilitated the frequency of the spontaneous or oxytocin-induced contractions in the pregnant rat and human uterus without altering the amplitude of these contractions. At high concentration of 200 mu m neocuproine could enhance the amplitude of the contractions in the pregnant uterus. These effects were blocked by a purinergic receptor antagonist, suramin (100 mu M) and did not occur following the administration of neocuproine-copper(I) complex or copper(II) chelator cuprizone. alpha,beta-methylene ATP increased the amplitude and frequency of contractions in the pregnant uterus, but not affected the contractions in the ovariectomized non-pregnant rat uterus, and neocuproine potentiated this facilitation effect. However, the suppressive effect of neocuproine on the ovariectomized non-pregnant rat uterus increased in the presence of alpha,beta-methylene ATP. beta-adrenoceptor blocker, propranolol or nitric oxide synthase inhibitor, L-nitroarginine did not affect the responses to neocuproine. These findings suggest that neocuproine can affect the uterus contractile activity by modulation purinergic excitatory responses and that copper(I)-sensitive mechanisms may play a role in this effect. (C) 2009 Elsevier B.V. All rights reserved.