Comparison of vasopressin binding sites in human uterine and vascular smooth muscle cells

Several studies indicate that oxytocin and vasopressin receptors in the hum an uterus are heterogeneous. We have investigated whether oxytocin and vaso pressin bind to separate receptors or one class of receptors in human uteri ne smooth muscle cells. [H-3]d(CH2)(5)Tyr(Me)AVP, the vasopressin V-1A rece ptor selective radioligand, was used for comparison of vasopressin binding sites in human uterine and vascular smooth muscle cell membranes. Both memb rane preparations exhibited one class of high-affinity binding sites with K -d values of 6.44 and 0.47 nM, B-max values of 166 and 34.8 fmol/mg protein for uterine and vascular smooth muscle cells, respectively. In vascular pr eparations, the selective vasopressin V-1A receptor antagonist, SR 49059 (( 2S) 1-[(2R 3S)-(5-chloro-3-(2-chlorophenyl)- 1-(3,4-dimethoxybenzenesulfony l)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide), showed high affinity with K-i value of 0.98 nM, confirming that these recep tors belong to the vasopressin V-1A receptor subtype. On the contrary, in u terine preparations, binding of [H-3]d(CH2)(5)Tyr(Me)AVP was more effective ly displaced by oxytocin and the oxytocin receptor selective antagonist, L- 371257, (1-{1-[4-[N-Acetyl-4-piperidinyl)oxy]2-methoxybenzoyl]piperidin-4-y l}-4H-3,1-benzoxazin-2(1H)-one), than vasopressin and SR 49059, suggesting that binding may be due to cross-reaction with the oxytocin receptors. Thes e results suggest that human uterine smooth muscle cells express only a hig h density of oxytocin receptors. (C) 1999 Elsevier Science B.V. All rights reserved.