LABELING OF VASOPRESSIN AND OXYTOCIN RECEPTORS FROM THE HUMAN UTERUS

Four labelled ligands, [H-3]arginine vasopressin ([H-3]AVP), [H-3]oxytocin ([H-3]OT), [H-3]d(CH2)5[Tyr(Me)2]AVP([H-3]VPA), and [I-125]d(CH2)5[ Tyr(Me)2-Thr4-Orn8-Tyr(NH2)9]OT([I-125]OTA)) and nine unlabelled analogues exhibiting enhanced selectivity for rat oxytocin (OT) and vasopressin (VP) receptors were used to characterize OT and VP receptors on myometrial membranes from non-pregnant and pregnant human uteri. On membranes from non-pregnant uteri, [H-3]AVP, [H-3]VPA, and [I-125]OTA labelled with high affinity (K(d) values: 3.2, 2 and 0.8 nM, respectively) a major and apparently homogeneous population of sites, the ligand selectivity of which resembled that of rat V1a VP receptors. On membranes from pregnant and non-pregnant uteri, [H-3]OT labelled a single population of high-affinity sites that could be distinguished from VP receptors on the basis of ligand selectivity. Several analogues (in particular [I-125]OTA) that are highly selective for rat OT receptors exhibited a much less pronounced selectivity for human OT receptors. Experiments with [H-3]VPA allowed detection of VP receptors on myometrical membranes from pregnant uteri and confirmed that only OT but not VP receptors increase during pregnancy in humans.