LOCALIZATION AND CHARACTERIZATION OF VASOPRESSIN BINDING-SITES IN THERAT-BRAIN USING AN IODINATED LINEAR AVP ANTAGONIST

The binding characteristics and central distribution of I-125-Linear A VP antagonist, a new ligand for vasopressin binding sites, are describ ed in the following studies. Saturation studies performed on rat brain septal membranes demonstrated that I-125-Linear AVP antagonist binds to a single class of sites with high affinity (55 pM) and limited capa city (88 fmol/mg protein). In autoradiographic studies, I-125-Linear A VP antagonist labeled brain areas known to contain vasopressin recepto rs without binding to neurophysins. I-125-Linear AVP antagonist also l abeled sites in cortex, hypothalamus, ventral tegmental area and subst antia nigra. In competition studies, I-125-Linear AVP antagonist bindi ng was most readily blocked by AVP and a selective V1a agonist. Oxytoc in and a selective V2 ligand were effective only in micromolar concent rations. A selective oxytocin agonist was virtually ineffective in blo cking I-125-Linear AVP antagonist binding. In regions that contain a h igh density of oxytocin binding sites, however, oxytocin-displaceable binding was observed. In agreement with studies on peripheral tissues, the binding profile generated from these studies indicates that I-125 -Linear AVP antagonist binds to vasopressin receptors of the V1a subty pe. These results suggest that I-125-Linear AVP antagonist is a valuab le ligand for the study of central AVP receptors.