Receptors for and myometrial responses to oxytocin and vasopressin in preterm and term human pregnancy: Effects of the oxytocin antagonist atosiban

Dec 1, 1994American journal of obstetrics and gynecology

Oxytocin and vasopressin receptors and muscle responses in early and full-term pregnancy: effects of the oxytocin blocker atosiban

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Abstract

The median concentration of oxytocin receptors in myometrial tissue was 116 fmol/mg protein in preterm patients not in labor.

Oxytocin receptor concentrations varied with labor status, reaching 134 fmol/mg protein at the beginning of labor and dropping to 46 fmol/mg protein in advanced labor for preterm deliveries.
At term, oxytocin receptor levels were 172 fmol/mg protein at the beginning of labor and 70 fmol/mg protein in advanced labor.
A decrease in V1 vasopressin receptor concentrations was also observed in advanced labor.
Oxytocin receptor concentrations correlated with the effects of oxytocin in vitro and the degree of inhibition by an oxytocin antagonist, but not with V1 vasopressin receptor concentrations.
No correlation was found between vasopressin response and concentrations of either oxytocin or V1 vasopressin receptors.

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OBJECTIVE: Our purpose was to study myometrial oxytocin and type V1 vasopressin receptors, the in vitro contractile effects of these hormones, and the influence of an oxytocin antagonist.

STUDY DESIGN: Women delivered by cesarean section preterm (n = 51) and at term (n = 71), with and without labor contractions, gave myometrium for the estimation of oxytocin and V1 vasopressin receptors. The in vitro myometrial effects of the peptides and the influence on these of the competitive oxytocin receptor blocking agent 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin were also tested.

RESULTS: The median concentration of oxytocin receptors was 116 fmol/mg protein (range 15 to 372 fmol/mg protein) in patients 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 concentrations were 172 (25 to 629), 223 (24 to 414), and 70 (21 to 92) fmol/mg protein. The concentration of V1 vasopressin receptors also decreased 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 treatment. Oxytocin receptors did not vary between women with different indications for cesarean section. The oxytocin effects in vitro and the degree of inhibition by the antagonist of oxytocin responses correlated with the concentration of oxytocin receptors but not with that of V1 vasopressin receptors. No correlation was seen between the response to vasopressin and concentrations of oxytocin or V1 vasopressin receptors.

CONCLUSIONS: The effect of oxytocin on the myometrium in pregnancy is mediated by an oxytocin receptor, whereas vasopressin acts on both oxytocin and vasopressin receptors. The initiation of labor both preterm and at term may be primarily related to increased release of oxytocin, which is locally produced in the uterus and not detectable in the plasma, but oxytocin and vasopressin receptors may play a role in the regulation of labor. The analog 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin, which blocks both the oxytocin and the V1 vasopressin receptor, should inhibit labor both preterm and at term, the former confirming results of recent clinical studies in Sweden and the United States.

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Receptors for and myometrial responses to oxytocin and vasopressin in preterm and term human pregnancy: Effects of the oxytocin antagonist atosiban

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