Urotensin II: A Novel Target in Human Corpus Cavernosum

Abstract

Urotensin II (U-II) is a cyclic peptide originally isolated from the teleost neurosecretory system and subsequently identified in other species, including man. U-II was identified as the natural ligand of an orphan G-protein coupled receptor (UT receptor). U-II and UT receptor are expressed in a variety of peripheral organs and especially in cardiovascular tissue. U-II caused both constrictor and vasodilator effect, depending by vascular bed. The in vivo functional consequences of U-II on the cardiovascular hemodynamics are not clearly understood. To investigate the presence of UT receptor and the effect of U-II in human corpus cavernosum (HCC) strips. To evaluate the effect of U-II in vivo in anesthetized rats. UT receptor expression as protein and as mRNA were assessed by Western blot and reverse transcriptase polymerase chain reaction. Next, the UT receptor localization was evaluated by immunohistochemical analysis. By using HCC strips, with or without endothelium, the effect of U-II (0.1 nM-10 microM) was evaluated. In order to asses the nitric oxide (NO) involvement, the strips were incubated with N (G)-nitro-L-arginine methyl ester (NO synthase inhibitor, 100 microM). U-II (0.1, 0.3, 1.0 nmol/rat) effect in vivo was studied in anesthetized rats by monitoring the intracavernous and systemic blood pressure. HCC expresses the UT receptor and its activation, by UII, causes an endothelium- and NO-dependent relaxation. UT receptor is expressed in human and rat corpus cavernosum. In HCC UT receptor is localized on endothelial cells. U-II significantly relaxed HCC strips in endothelium- and -NO-dependent fashion. The peptide caused a significant increase in intracavernous pressure in anesthetized rats. This study demonstrates that UT receptor is expressed on the endothelium of HCC. U-II/UT receptor system is involved in HCC function and it involves endothelium and NO pathway. Thus, U-II/UT receptor pathway could be involved in erectile function.