title: Effects of nociceptin and nocistatin on uterine contraction.
abstract: The presence and effects of nociceptin (N/OFQ) and nocistatin (NST) in the central nervous system have been reasonably well described, but less data are available on their peripheral functions. Besides their presence in several peripheral organs (white blood cells, airway, liver, skin, vascular and intestinal smooth muscles, ovary, and testis), they have been found in the pregnant myometrium in both rat and human. The level of their precursor prepronociceptin is elevated in the preterm human myometrium as compared with full-term samples, whereas it gradually increases toward term in the pregnant rat uterus. Both N/OFQ and NST inhibit myometrial contractions, an effect which can be enhanced by naloxone and blocked by Ca²⁺-dependent K⁺ channel (BK(Ca)) inhibitors. Both compounds increase the myometrial cAMP level which may be responsible for the activation of this channel and subsequent intracellular hyperpolarization. NST releases calcitonin gene-related peptide from the sensory nerve ends, which explains its cAMP-elevating effect. In contrast with the nervous system, where they behave as antagonists, N/OFQ and NST are able to potentiate the uterine-relaxing effect of each other in both rat and human tissues. Further studies are required to clarify the roles of N/OFQ and NST in the regulation of the myometrial contractions and the perception of pain during delivery.
authors: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary. Electronic address: gaspar@pharm.u-szeged.hu.
authors: Róbert
authors: R
authors: Gáspár
authors: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
authors: Beáta H
authors: BH
authors: Deák
authors: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
authors: Anna
authors: A
authors: Klukovits
authors: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
authors: Eszter
authors: E
authors: Ducza
authors: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
authors: Kornélia
authors: K
authors: Tekes
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D008954:Models, Biological; D009215:Myometrium / Q000378:metabolism; D018847:Opioid Peptides / Q000378:metabolism*; D009928:Organ Specificity; D011247:Pregnancy; D014590:Uterine Contraction / Q000378:metabolism*; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D000097629:Nociceptin; C111148:nocistatin
keywords: Calcitonin gene-related peptide; Calcium-dependent potassium channels; Cyclic adenosine moNOP-phosphate; Human; Nociceptin; Nocistatin; Pregnant myometrium; Preterm; Rat