title: Binding of [3H] SR 49059, a potent nonpeptide vasopressin V1a antagonist, to rat and human liver membranes.
abstract: The new potent and selective nonpeptide vasopressin V1a antagonist, SR 49059, was tritiated and used for the characterization of rat and human liver AVP V1a receptors. Binding of [3H] SR 49059 was time-dependent, reversible and saturable. A single class of high affinity binding sites was identified with Kd values of 0.63 +/- 0.13 and 2.95 +/- 0.64 nM, in rat and human liver membranes, respectively. The maximal binding capacity (Bmax) was about 7 times higher in rat than in human liver preparations. The relative potencies of several AVP/oxytocin agonists or antagonists to inhibit [3H] SR 49059 binding confirmed that this ligand labeled a homogeneous population of sites with the expected AVP V1a profile. Furthermore, [3H] SR 49059 or unlabeled SR 49059 displayed only slight species differences between rat and human V1a receptors, whereas OPC-21268, another nonpeptide V1a antagonist, exhibited a high species-related potency with more than 500 fold higher affinity for rat than for human liver V1a receptors. Thus, [3H] SR 49059 is the first nonpeptide AVP V1a ligand reported having highly specific activity, stability, specificity and affinity. This makes it a suitable probe for labeling AVP V1a receptors in rat and also in human tissues.
authors.affiliation: Sanofi Recherche, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Serradeil-Le Gal
authors.forename: D
authors.initials: D
authors.lastname: Raufaste
authors.forename: E
authors.initials: E
authors.lastname: Marty
authors.forename: C
authors.initials: C
authors.lastname: Garcia
authors.forename: J P
authors.initials: JP
authors.lastname: Maffrand
authors.forename: G
authors.initials: G
authors.lastname: Le Fur
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors*; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011759:Pyrrolidines / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism*
chemical_list: D007211:Indoles; D011759:Pyrrolidines; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C082134:relcovaptan