Oxytocin Antagonist (dTVT) and Oxytocin Receptors in Myometrium and Decidua

ABSTRACT

To investigate whether a putative oxytocin (OT) receptor blocker 1-deamino-[2-D-tyrosine (OEt)-4 threonine-8-ornithine]oxytocin (dTVT) inhibits OT binding to its receptors, we studied binding of [³H]OT to late-pregnant human, guinea pig, and rat myometrial and decidual membranes and competition of dTVT with this binding. Deciduaas well as myometrium of all three species bound [³H]OT with high affinity (K_d 1-3 nM) and limited capacity. The concentration of binding sites in decidual membranes was slightly lower than in myometrial membranes in human and guinea pig uterus and twice that of myometrial membranes in day 20 pregnant rat uterus. dTVT competed with [³H]OT with highest affinity in guinea pig myomterium and decidua, the potency ratios ([dTVT]₅₀ : [OT]₅₀) being 1.9 and 3.3, respectively. The potency ratios in rat uterine tissues and human decidua were slightly higher (4 to 5) and highest in human myometrium, 23.3. Excess dTVT completely inhibited [³H]OT binding in all six tissues, indicating binding to the same receptor sites. Because of the high-affinity binding of dTVT to oxytocin receptors in human decidua and myometrium, this oxytocin analogue may be a very effective tocolytic agent in the treatment of threatened preterm labor.