OXYTOCIN AND VASOPRESSIN IN UTERINE ACTIVITY. Receptor-mediated agonism and antagonism with special regard to the aetiology and treatment of preterm labour and primary dysmenorrhoea
Sammanfattning: With a view to the aetiology and treatment of preterm labour and primary dysmenorrhoea we studied the influence of sexual steroids on the plasma levels of oxytocin and vasopressin, effect of these peptides on uterine contractility in vitro and in vivo, receptor concentrations and antagonists to oxytocin and vasopressin. In postmenopausal women oestrogen increased the concentrations in plasma of both peptides, whereas progesterone increased oxytocin but decreased vasopressin levels. In pregnant women no increase in oxytocin or vasopressin V1a receptors was seen at the onset of labour and concentrations did not differ between women delivered preterm or at term. In advanced labour the oxytocin receptor decreased. Inhibition in vitro of the antagonist 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin correlated to the concentration of the oxytocin receptor. Vasopressin had a higher effect than oxytocin in non-pregnant women, particularly before menstruation. In both pregnant and non-pregnant state, myometrial effects and receptor-concentrations to oxytocin correlated, but not those to vasopressin. SR 49059 inhibited vasopressin-induced myometrial activity in vitro and in women during menstruation. Up-regulation of oxytocin receptors does not seem to cause the start of labour preterm or at term, but a down-regulation by oxytocin itself may occur. Oxytocin acts specifically via its own receptor whereas vasopressin acts via both receptors. The findings regarding 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin supports its therapeutic action in preterm labour and a role for oxytocin in the onset of labour. SR 49059 is a selective V1a receptor antagonist and may be a valuable tool for studying the role of vasopressin in the mechanisms of primary dysmenorrhoea.
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