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 e)(2)Phe(3)-Gln(4)-A sn(5)-Arg(6)-Pro(7)-Arg(8)-NH2 (HO-LVA). Iodinated on the phenolic sub stituent at position 1,[I-125]-HO-LVA displayed the highest affinity f or rat liver V-1a receptors (8 pM) ever reported. Furthermore, affinit ies of HO-LVA and I-HO-LVA for V-1b, V-2 and oxytocin (OT) receptors w as 400- to 1,000-fold lower than for V-1a receptors, rendering it a hi ghly 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 pot ency, the AVP-induced ACTH release from freshly prepared pituitary cel ls. Using autoradiography [I-125]-HO-LVA appeared to be the first radi oligand to successfully identify and localize the presence of V-1a rec eptors in rat liver and blood vessel walls. Moreover, several new brai n regions expressing V-1a receptors could be identified, in addition t o those brain regions that were previously identified with other radio labelled AVP analogues.