Localization and characterization of vasopressin binding sites in the rat brain using an iodinated linear AVP antagonist.

The binding characteristics and central distribution of 125I-Linear AVP antagonist, a new ligand for vasopressin binding sites, are described in the following studies. Saturation studies performed on rat brain septal membranes demonstrated that 125I-Linear AVP antagonist binds to a single class of sites with high affinity (55 pM) and limited capacity (88 fmol/mg protein). In autoradiographic studies, 125I-Linear AVP antagonist labeled brain areas known to contain vasopressin receptors without binding to neurophysins. 125I-Linear AVP antagonist also labeled sites in cortex, hypothalamus, ventral tegmental area and substantia nigra. In competition studies, 125I-Linear AVP antagonist binding was most readily blocked by AVP and a selective V1a agonist. Oxytocin and a selective V2 ligand were effective only in micromolar concentrations. A selective oxytocin agonist was virtually ineffective in blocking 125I-Linear AVP antagonist binding. In regions that contain a high 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 125I-Linear AVP antagonist binds to vasopressin receptors of the V1a subtype. These results suggest that 125I-Linear AVP antagonist is a valuable ligand for the study of central AVP receptors.