Uterus-Relaxing Effects of Nociceptin and Nocistatin: Studies on Preterm and Term-Pregnant Human Myometrium In vitro

Abstract

The endogenous neuropeptides nociceptin/orphanin FQ and nocistatin translated from the prepronociceptin gene exert a relaxant effect on the rat uterus. Previous studies have reported their role in pain transmission in the central nervous system both in rodents and in humans, but to date only limited information is available on their effects in the periphery, and there are no data on their presence in the human uterus. The expression of prepronociceptin mRNA in the human uterus was confirmed by an RT-PCR technique. In vitro contractility studies of the action of nociceptin and nocistatin on human uterine tissues were performed in an isolated organ system. Human myometrial strips from cesarean sections at full-term pregnancy and at preterm labor were stimulated with oxytocin, and the relaxant effects of nociceptin and nocistatin were studied. The level of prepronociceptin mRNA was significantly decreased in full-term pregnant uterus samples as compared with preterm pregnancy samples. Nociceptin and nocistatin significantly and dose-dependently inhibited the oxytocinevoked contractions in the human uterus. In the presence of nocistatin, the uterus-relaxant effect of nociceptin was enhanced. In contrast, nociceptin did not alter the uterus-relaxant effect of nocistatin. We conclude that locally generated nociceptin and nocistatin both exert a relaxant effect on the human uterus, and nocistatin can potentiate the relaxant effect of nociceptin, though for this to occur nocistatin administration must precede the administration of nociceptin.