Characterization Of A Novel, Linear Radioiodinated Vasopressin Antagonist - An Excellent Radioligand For Vasopressin V-1a Receptors

We report on the pharmacological properties of a potent and selective linear vasopressin (AVP) V-1a receptor antagonist HO-Phenylacetyl(1)-D-Tyr(Me)(2)Phe(3)-Gln(4)-Asn(5)-Arg(6)-Pro(7)-Arg(8)-NH2 (HO-LVA). Iodinated on the phenolic substituent at position 1,[I-125]-HO-LVA displayed the highest affinity for rat liver V-1a receptors (8 pM) ever reported. Furthermore, affinities of HO-LVA and I-HO-LVA for V-1b, V-2 and oxytocin (OT) receptors was 400- to 1,000-fold lower than for V-1a receptors, rendering it a highly selective ligand. Both HO-LVA and its iodinated derivative are V-1 antagonists, they potently inhibited AVP-induced inositol-phosphate accumulation in WRK(1) cells, and also, although with a much lower potency, the AVP-induced ACTH release from freshly prepared pituitary cells. Using autoradiography [I-125]-HO-LVA appeared to be the first radioligand to successfully identify and localize the presence of V-1a receptors in rat liver and blood vessel walls. Moreover, several new brain regions expressing V-1a receptors could be identified, in addition to those brain regions that were previously identified with other radiolabelled AVP analogues.