Identification and characterization of binding sites for human urotensin-II in Sprague–Dawley rat renal medulla using quantitative receptor autoradiography

Urotensin-II (U-II), a ligand for the G-protein-coupled receptor UT, has been characterized as the most potent mammalian vasoconstrictor identified to date. Although circulating levels of U-II are altered in lower species (e.g., fish) upon exposure to hypo-osmotic stress, little is known about the actions of this cyclic undecapeptide within the kidney, an organ that plays a pivotal role in the control of cardiovascular homeostasis, influencing both cardiac preload (plasma volume) and after load (peripheral resistance). The present study reports the identification of specific, high affinity [125I]hU-II binding sites in Sprague–Dawley rat kidney outer medulla by autoradiography and also through membrane radioligand binding (Kd 1.9 ± 0.9 nM and Bmax 408 ± 47 amol mm−2 and Kd 1.4 ± 0.3 nM and Bmax 51.3 ± 7.8 fmol mg−1 protein, respectively). Differences were observed in the binding characteristics within rat strains. Compared to the Sprague–Dawley, Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rat kidney outer medulla displayed low density <20 fmol mg−1 protein and low affinity (>1 μM) [125I]hU-II binding sites. Thus, the relative contribution of specific U-II binding sites to the physiological actions of U-II in the control of cardiorenal homeostasis is worthy of further investigation.