Pharmacological characterization of F-180:: a selective human V1a vasopressin receptor agonist of high affinity

1 The pharmacological properties of F-180, a vasopressin (VP) structural analogue, were determined on CHO cells expressing the different human vasopressin and oxytocin (OT) receptor subtypes. Binding experiments revealed that F-180 exhibited a high affinity for the human Via receptor subtype (K-i = 11 nM) and was selective for this receptor subtype. 2 Functional studies performed on CHO cells expressing human Via receptors indicate that similarly to AVP, F-180 can stimulate the accumulation of inositol phosphate. The activation constant (K-act) for both F-180 and AVP was 1.7 nm. F-180 was also an agonist for the human V-2 and V-1b receptor subtypes and an antagonist for the human OT receptor. 3 Since marked species pharmacological differences for vasopressin receptors have been described, we studied the properties of F-180 on various mammalian species. F-180 showed high affinity and good selectivity for human and bovine Via receptors, but weak affinity and non selective properties for rat Via receptors. 4 To assess the functional properties of F-180 on a native biological model, we performed studies on primary cultures of cells from bovine zona fasciculata (ZF). As AVP, F-180 stimulated inositol phosphate accumulation and cortisol secretion with similar efficiency. 5 In conclusion, we demonstrate that F-180 is the first selective Via agonist described for human and bovine vasopressin receptors. Therefore F-180 can be used as a powerful pharmacological tool to characterize the actions of vasopressin that are mediated by Via receptor subtypes. British Journal of Pharmacology.