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• W2005039156 abstract "A possible role of arginine vasopressin (AVP) V 1b receptor subtype in stress‐related disorders has been recently highlighted by the discovery of the agonist [1‐deamino‐4‐cyclohexylalanine] AVP (d[Cha 4 ]AVP) and the antagonist SSR149415. Both compounds have been proposed to target specifically V 1b receptors, since the reported affinities for the related V 1a , V 2 and oxytocin receptors are in the micromolar or submicromolar range. In the present study, we further investigated the binding affinities of d[Cha 4 ]AVP and SSR149415 at recombinant human vasopressin V 1b (hV 1b ) and oxytocin (hOT) receptors expressed in Chinese hamster ovary (CHO) cells and functional properties of both compounds at hV 1b , hV 1a , hV 2 and hOT receptors. d[Cha 4 ]AVP bound to hV 1b receptors and hOT receptors with p K i values of 9.68±0.06 and 7.68±0.09, respectively. SSR149415 showed p K i values of 9.34±0.06 at hV 1b and 8.82±0.16 at hOT receptors. d[Cha 4 ]AVP stimulated [Ca 2+ ] i increase in hV 1b ‐CHO cells with a pEC 50 value of 10.05±0.15. It showed pEC 50 values of 6.53±0.17 and 5.92±0.02 at hV 1a and hV 2 receptors, respectively, and behaved as a weak antagonist at hOT receptors (p K B =6.31±0.12). SSR149415 inhibited the agonist‐induced [Ca 2+ ] i increase with p K B values of 9.19±0.07 in hV 1b ‐CHO and 8.72±0.15 in hOT‐CHO cells. A functional p K i value of 7.23±0.10 was found for SSR1494151 at hV 1a receptors, whereas it did not inhibit 20 n M AVP response at hV 2 receptors up to 3 μ M . Data obtained confirmed the high potency and selectivity of d[Cha 4 ]AVP at hV 1b receptors, but revealed that SSR149415, in addition to the high potency at hV 1b receptors, displays a significant antagonism at hOT receptors. British Journal of Pharmacology (2005) 146 , 744–751. doi: 10.1038/sj.bjp.0706383" @default.
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• W2005039156 date "2005-11-01" @default.
• W2005039156 modified "2023-10-17" @default.
• W2005039156 title "Selectivity of d[Cha⁴ ]AVP and SSR149415 at human vasopressin and oxytocin receptors: evidence that SSR149415 is a mixed vasopressin V_1b /oxytocin receptor antagonist" @default.
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• W2005039156 doi "https://doi.org/10.1038/sj.bjp.0706383" @default.
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