title: The D136A mutation of the V2 vasopressin receptor induces a constitutive activity which permits discrimination between antagonists with partial agonist and inverse agonist activities.
abstract: The substitution, in the human V2 vasopressin receptor, of the aspartate at position 136 by alanine leads to agonist-independent activation of this mutant V2 receptor. Pharmacological studies of the D136A V2 receptor helped us in characterizing different V2 receptor antagonists. SR-121463A and OPC-31260, two non-peptide antagonists, behaved as inverse agonists, while two cyclic peptides d(CH2)5[D-Tyr(Et)2,-Val4,Tyr-NH(2)9]AVP and d(CH2)5[D-Ile2,Ile4,Tyr-NH(2)9]AVP known to be V2 antagonists, demonstrated clear partial agonist properties. The finding of a constitutively activated human V2 receptor represents a useful tool in characterizing V2 receptor antagonist ligands.
authors.affiliation: Unité INSERM 469, CCIPE, Montpellier, France. morin@u469.montp.inserm.fr
authors.forename: D
authors.initials: D
authors.lastname: Morin
authors.forename: N
authors.initials: N
authors.lastname: Cotte
authors.forename: M N
authors.initials: MN
authors.lastname: Balestre
authors.forename: B
authors.initials: B
authors.lastname: Mouillac
authors.forename: M
authors.initials: M
authors.lastname: Manning
authors.forename: C
authors.initials: C
authors.lastname: Breton
authors.forename: C
authors.initials: C
authors.lastname: Barberis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D019556:COS Cells; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D017483:Receptors, Vasopressin / Q000819:agonists / Q000235:genetics*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D000242:Cyclic AMP