RECEPTORS FOR AND MYOMETRIAL RESPONSES TO OXYTOCIN AND VASOPRESSIN INPRETERM AND TERM HUMAN-PREGNANCY - EFFECTS OF THE OXYTOCIN ANTAGONISTATOSIBAN

OBJECTIVE: Our purpose was to study myometrial oxytocin and type V1 va sopressin receptors, the in vitro contractile effects of these hormone s, and the influence of an oxytocin antagonist. STUDY DESIGN: Women de livered by cesarean section preterm (n = 51) and at term (n = 71), wit h and without labor contractions, gave myometrium for the estimation o f oxytocin and V1 vasopressin receptors. The in vitro myometrial effec ts of the peptides and the influence on these of the competitive oxyto cin receptor blocking agent 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytoci n were also tested. RESULTS: The median concentration of oxytocin rece ptors was 116 fmol/mg protein (range 15 to 372 fmol/mg protein) in pat ients delivered preterm not in labor, 134 fmol/mg protein (27 to 1421 fmol/mg protein) in the beginning of labor, and 46 fmol/mg protein (9 to 140 fmol/mg protein) in advanced labor. At term the corresponding c oncentrations were 172 (25 to 629), 223 (24 to 414), and 70 (21 to 92) fmol/mg protein. The concentration of VI vasopressin receptors also d ecreased in advanced labor. In advanced labor after oxytocin infusion a reduction in the concentration of the receptor for this hormone was observed, which appeared to be related to the duration and dose of tre atment. Oxytocin receptors did not vary between women with different i ndications for cesarean section. The oxytocin effects in vitro and the degree of inhibition by the antagonist of oxytocin responses correlat ed with the concentration of oxytocin receptors but not with that of V 1 vasopressin receptors. No correlation was seen between the response to vasopressin and concentrations of oxytocin or V1 vasopressin recept ors. CONCLUSIONS: The effect of oxytocin on the myometrium in pregnanc y is mediated by an oxytocin receptor, whereas vasopressin acts on bot h oxytocin and vasopressin receptors. The initiation of labor both pre term and at term may be primarily related to increased release of oxyt ocin, which is locally produced in the uterus and not detectable in th e plasma, but oxytocin and vasopressin receptors may play a role in th e regulation of labor. The analog 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-o xyto which blocks both the oxytocin and the V1 vasopressin receptor, s hould inhibit labor both preterm and at term, the former confirming re sults of recent clinical studies in Sweden and the United States.