1-desamino-8-D-arginine vasopressin (DDAVP) as an agonist on V-1b vasopressin receptor

1 desamino-8-D-arginine vasopressin (DDAVP) is considered a standard vasopressin V-2 receptor-selective agonist with a patent antidiuretic effect through V-2 receptor without the induction of vasoconstriction through V-1a receptor. Furthermore, DDAVP was reported to act as an agonist on non-V-1a, non-V-2 receptor to cause the accumulation of intracellular Ca2+ in several tissues. However, the agonistic activity of DDAVP against the other vasopressin receptor, V-1b (Or V-3), which can accumulate intracellular Ca2+ and which we recently cloned, has not been clarified. Hence, we compared the characteristics of DDAVP on V(1)b receptor with those on the other vasopressin receptors. In binding experiments, DDAVP more strongly inhibited [H-3]arginine vasopressin binding to V-1b than to V-2 receptor (K-1: 5.84 nM vs 65.9 nM). In addition, DDAVP dose-dependently stimulated inositol turnover in human V-1b receptor-expressing COS-1 cells. DDAVP acted as a full agonist on human V-1b receptor (EC50: 11.4 nM) as well as on human V-2 receptor (EC50: 23.9 nM). However, DDAVP behaved as a partial agonist toward rat V-1b receptor (intrinsic activity: 0.7, EC50: 43.5 nM), while there was no significant difference in the agonistic properties of arginine vasopressin on human and rat V-1b receptor. In conclusion, DDAVP acts as an agonist on V-1b receptor, as it does on V-2 receptor. These findings will allow us to better understand the physiological role of V-1b receptor in pancreatic beta cells and in the renal inner medullary collecting duct, and help us to identify as yet unknown vasopressin receptors through which DDAVP cause the accumulation of intracellular Ca2+ in other tissues. (C) 1997 Elsevier Science Inc.