Biological characterization of rodent and human vasopressin V1b receptors using SSR-149415, a nonpeptide V1b receptor ligand

[3H]SSR-149415 is the first tritiated nonpeptide vasopressin V1b receptor (V1bR) antagonist ligand. It was used for studying rodent (mouse, rat, hamster) and human V1bR from native or recombinant origin. Moreover, a close comparison between the human and the mouse V1bR was performed using SSR-149415/[3H]SSR-149415 in binding and functional studies in vitro. [3H]SSR-149415 binding was time-dependent, reversible, and saturable. Scatchard plot analysis gave a single class of high-affinity binding sites with apparent equilibrium dissociation constant (Kd) ∼1 nM and maximum binding density (Bmax) values from 7,000 to 300,000 sites/cell according to the cell line. In competition experiments, [3H]SSR-149415 binding was stereospecific and dose-dependently displaced by reference peptide and nonpeptide arginine vasopressin (AVP)/OT ligands following a V1b rank order of affinity: SSR-149415 = AVP > dCha > dPen > dPal > dDavp > SSR-126768A > SR-49059 > SSR-149424 > OT > SR-121463B. Species differences between human, ...