The D136A mutation of the V2 vasopressin receptor induces a constitutive activity which permits discrimination between antagonists with partial agonist and inverse agonist activities
Morin, D.; Cotte, N.; Balestre, M.N.; Mouillac, B.; Manning, M.; Breton, C.; Barberis, C.
Febs Letters 441(3): 470-475
ISSN/ISBN: 0014-5793 PMID: 9891993 DOI: 10.1016/s0014-5793(98)01585-3
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.