Autoradiographic localization of vasopressin V(1a) receptors in the rat kidney using [3H]-SR 49059

Abstract

Localization and characterization of binding sites of the selective non-peptide vasopressin receptor V(1a) ligand, [3H]-SR 49059, were investigated in the adult rat kidney by quantitative autoradiography using a fast-detecting radioluminographic phosphor-imaging plate system. [3H]-SR 49059, like the other V(1a) ligands used, showed a total absence of binding in the papilla, discrete and sparse labeling in the cortex and maximal binding in the outer part of the inner medulla. This labeling seemed to be mainly associated with medullary interstitial cells and vascular elements of the vasa recta. Conversely, [3H]-AVP intensely labeled the V2-enriched medullo-papillary portion of the kidney and, to a lesser extent, the cortical structures [3H]-SR 49059 binding, quantified in the outer part of the inner medulla in rat kidney sections, was time-dependent, reversible, saturable and a single class of high affinity binding sites, (K(d) = 1.48 ± 0.16 nM) was identified. The relative potencies of the reference peptide and non-peptide compounds to inhibit [3H]-SR 49059 binding confirm the V(1a) nature of the site and the stereospecificity of this binding. Thus, [3H]- SR 49059 allows the mapping and characterization of the V(1a) receptor population present in the rat kidney. The stability and the highly selective affinity of this non-peptide ligand for rat and human V(1a) receptors make it a suitable probe for the localization of V(1a) receptors in organs expressing heterogenous populations of receptors.