COMPARISON OF VASOPRESSIN AND OXYTOCIN RECEPTORS IN THE RAT UTERUS AND VASCULAR TISSUE

Several studies indicate that oxytocin and vasopressin receptors in th e human uterus are heterogeneous. We have investigated whether oxytoci n and vasopressin bind to separate receptors in the day 21 and day 22 pregnant rat uterus and whether uterine vasopressin receptors are the same as the vascular V-1A subtype. In isolated organ bath experiments we showed that the potency of d(CH2)(5)[Tyr(Me)(2)]vasopressin to inhi bit vasopressin contraction in rat aorta was different from that in th e day 21 pregnant uterus. Saturation curves of [H-3]vasopressin in mem branes from cultured aortic myocytes and pregnant uterus were linear a nd yielded the same 1 nM K-d values. However, the potency of d(CH2)(5) [Tyr(Me)(2)]vasopressin and of [Thr(4),Gly(7)]oxytocin at antagonizing [H-3]vasopressin confirmed the differences between the vascular smoot h muscle and uterine vasopressin receptor. The peptides had respective ly higher and lower affinity for aortic cell sites than for uterine si tes. It was more difficult to distinguish pharmacological differences for oxytocin and vasopressin receptors in the uterus. On day 22, the h igh affinity of [Thr(4),Gly(7)]oxytocin and oxytocin for both [H-3]oxy tocin and [H-3]vasopressin binding sites was consistent with the notio n that the uterus expresses essentially oxytocin receptors at this sta ge of gestation. However, oxytocin, vasopressin and three analogs show ed a different potency for inhibiting [H-3]oxytocin and [H-3]vasopress in binding on day 21 versus day 22 of gestation. We conclude that in t he rat uterus vasopressin binds to a receptor that is different from t he vascular V-1A subtype. Also, the binding sites for [H-3]vasopressin and [H-3]oxytocin on day 21 uterus membranes do not resemble the clas sical oxytocin receptor as described in the literature, suggesting tha t on day 21 vasopressin and oxytocin bind in the uterus to a receptor that might be different from those currently characterized.