Human Myometrium during Pregnancy Contains and Responds to VI Vasopressin Receptors as well as Oxytocin Receptors*

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Abstract
We have recently demonstrated the presence of two classes of neurophypophysial hormone receptors in the vagina, myometrium, and oviduct of rabbit: an oxytocin (OT) site and a V1 arginine vasopressin (AVP) site. We now report binding and in vitro contractility studies on human myometrial specimens obtained at cesarean section from women at the end of pregnancy. The program Ligand was used to analyze self- and cross-displacement curves for labeled OT, AVP or its V1 antagonist d(CH2)5TyrMeAVP, the corresponding unlabeled peptides, and selective analogs. Our results clearly indicate the presence of heterogeneity of binding sites in human uterus. Blocking experiments were performed to evaluate the density of OT and V1 AVP receptors in individual uterine specimens. The contractile response of the same samples to OT, AVP, and analogs was also evaluated. Our results indicate that V1 AVP receptors are present in all of the uterine specimens investigated, with virtually equal density from 32 weeks to term. AVP and the V1-selective agonist [Phe2,Ile3,Orn8]VP stimulate contractility of uterine strips, an effect blocked by nanomolar concentration of the V1 antagonist d(CH2)5TyrMeAVP. Uterine OT receptors increase during late pregnancy, peaking in early labor. A significant correlation between the density of OT receptors and the frequency of uterine contractions (external tocorgraphy) was found in pregnant women before surgery. OT stimulated in vitro contractility of uterine strips only when the density of receptors was more than 150 fmol/mg protein. In conclusion, we identified biologically active V1 AVP receptors in human uterus at the end of gestation and confirmed the primary relevance of OT receptors in human parturition.