Comparison of vasopressin and oxytocin receptors in the rat uterus and vascular tissue

Several studies indicate that oxytocin and vasopressin receptors in the human uterus are heterogeneous. We have investigated whether oxytocin 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 inhibit vasopressin contraction in rat aorta was different from that in the day 21 pregnant uterus. Saturation curves of [H-3]vasopressin in membranes from cultured aortic myocytes and pregnant uterus were linear and 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 smooth muscle and uterine vasopressin receptor. The peptides had respectively higher and lower affinity for aortic cell sites than for uterine sites. It was more difficult to distinguish pharmacological differences for oxytocin and vasopressin receptors in the uterus. On day 22, the high affinity of [Thr(4),Gly(7)]oxytocin and oxytocin for both [H-3]oxytocin and [H-3]vasopressin binding sites was consistent with the notion that the uterus expresses essentially oxytocin receptors at this stage of gestation. However, oxytocin, vasopressin and three analogs showed a different potency for inhibiting [H-3]oxytocin and [H-3]vasopressin binding on day 21 versus day 22 of gestation. We conclude that in the rat uterus vasopressin binds to a receptor that is different from the 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 classical oxytocin receptor as described in the literature, suggesting that on day 21 vasopressin and oxytocin bind in the uterus to a receptor that might be different from those currently characterized.