Objective To test binding affinities for, and inhibitory effects on, myometrium of some oxytocin and vasopressin antagonists with respect to their therapeutic potential.Design Receptor binding studies on transfected cell lines. In vifro contractility studies of human myometrium.Setting The Research Laboratory of Sanofi Recherche, Centre de Toulouse, France and the Departments of Obstetrics and Gynecology, Lund University Hospital, Sweden and Bialystok University Hospital, Poland.Participants Nine women delivered by caesarean section preterm and 37 delivered at term for routine obstetric indications. Results Oxytocin had a high affinity for the oxytocin receptor (K, in mean = 6.8 nmoYL) and bound, to some extent, to the vasopressin V,, receptor (K, = 34.9 nmol/L). Vasopressin displayed higher affinities for vasopressin V,,, V,, and V2 receptors (Ki = 1.4,0-8 and 4.2 nmovL, respectively) than for the oxytocin receptor (Ki = 48 nmoliL). Atosiban and SR 49059 both had a high affinity for the vasopressin V,, receptor (Ki = 4.7 and 7.2 nmoVL, respectively, and a moderate one for the oxytocin receptor (Ki = 397 and 340 nmoVL, respectively). SR 121463 exerted a predominant binding to the V, receptor (K, = 3-0 nmoVL). In the concentration-response experiments levels of up to 10 nmol/L of SR 49059 had no influence on the effect of oxytocin on myometrium from women preterm and at term pregnancy. However, a concentration-dependent inhibition of the responses of both these type of tissues to vasopressin was seen. The effects of EC,o concentrations of oxytocin and vasopressin on term pregnant myometrium were markedly inhibited by 10 nmovL and higher concentrations of SR 49059, the inhibition of the response to vasopressin being more pronounced than that of the oxytocin response. SR 121463 at maximal concentration only caused slight inhibitions of the oxytocin and vasopressin responses. InterventionsConclusions Atosiban and SR 49059 both have moderate binding affinities for the human oxytocin receptor and high binding affinities for the vasopressin V,, one. We demonstrated that SR 49059 inhibits the response of term myometrium to oxytocin and that of both preterm and term myometrium to vasopressin. These observations suggest a therapeutic potential of SR 49059 in preterm labour. The vasopressin V, receptor is apparently not involved to any significant degree in the activation of the pregnant human uterus.

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Robot assisted laparoscopic radical hysterectomy is a feasible alternative to conventional laparoscopy and open surgery. Effort should be made to ensure proper closure of the vaginal cuff, trocar sites and to develop nerve sparing techniques.

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Objective To study in nonpregnant women myometrial actions of vasopressin and oxytocin and Subjects Twenty-eight women undergoing hysterectomy for benign gynaecological disorders. Interventions Intrauterine pressure recordings. Intravenous bolus injections of 10 pmol/kg body weight of vasopressin and oxytocin. Repeated blood sampling for measurement of vasopressin and oxytocin concentrations in plasma. Recording of effects of vasopressin and oxytocin on isolated myometrium. Estimation of myometrial concentrations of vasopressin V 1 a and oxytocin receptors. Measurement of plasma oestradiol and progesterone. Main outcome measures Vasopressin-and oxytocin-induced increases of the area under the in vivo recording curve over 10 minutes and EC,, concentrations of dose-responses in vitro. Concentrations of vasopressin Vla and oxytocin receptors. ResultsVasopressin was on average four times more potent than oxytocin in vivo. The effect of vasopressin premenstrually was more pronounced than in women under oestrogen influence only (proliferative phase-hyperproliferation; P = 0.02), and tended to be more marked than in those in the luteal phase (P = 0.07). No significant variation in oxytocin response with the hormonal state was observed. EC,, concentrations of vasopressin were more than 20 times lower than those of oxytocin. The median concentration of the vasopressin Vla receptor was 208 (range 139-343) fmol/mg protein and that of the oxytocin receptor 49 (38-87) fmol/mg protein. Vasopressin receptor concentrations and in vivo effects of this peptide did not correlate, whereas for those of oxytocin a significant correlation was observed (P = 0.02). ConclusionThe high potency of vasopressin in nonpregnant women, particularly premenstrually, firmly supports an aetiological importance of this peptide in the uterine hyperactivity of primary dysmenorrhoea. Oxytocin seems to be less important in this condition in view of its much smaller potency and the absence of increase in effect premenstrually. Vasopressin appears to influence both the oxytocin and the vasopressin Vla receptor sites in the uterus, whereas oxytocin acts specifically on its own receptor.