Endogenous urotensin II selectively modulates erectile function through eNOS.
BACKGROUND
Urotensin II (U-II) is a cyclic peptide originally isolated from the neurosecretory system of the teleost fish and subsequently found in other species, including man. U-II was identified as the natural ligand of a G-protein coupled receptor, namely UT receptor. U-II and UT receptor are expressed in a variety of peripheral organs and especially in cardiovascular tissue. Recent evidence indicates the involvement of U-II/UT pathway in penile function in human, but the molecular mechanism is still unclear. On these bases the aim of this study is to investigate the mechanism(s) of U-II-induced relaxation in human corpus cavernosum and its relationship with L-arginine/Nitric oxide (NO) pathway.


RESULTS
Human corpus cavernosum tissue was obtained following in male-to-female transsexuals undergoing surgical procedure for sex reassignment. Quantitative RT-PCR clearly demonstrated the U-II expression in human corpus cavernosum. U-II (0.1 nM-10 µM) challenge in human corpus cavernosum induced a significant increase in NO production as revealed by fluorometric analysis. NO generation was coupled to a marked increase in the ratio eNOS phosphorilated/eNOS as determined by western blot analysis. A functional study in human corpus cavernosum strips was performed to asses eNOS involvement in U-II-induced relaxation by using a pharmacological modulation. Pre-treatment with both wortmannin or geldanamycinin (inhibitors of eNOS phosphorylation and heath shock protein 90 recruitment, respectively) significantly reduced U-II-induced relaxation (0.1 nM-10 µM) in human corpus cavernosum strips. Finally, a co-immunoprecipitation study demonstrated that UT receptor and eNOS co-immunoprecipitate following U-II challenge of human corpus cavernosum tissue.


CONCLUSIONS
U-II is endogenously synthesized and locally released in human corpus cavernosum. U-II elicited penile erection through eNOS activation. Thus, U-II/UT pathway may represent a novel therapeutical target in erectile dysfunction.
Interdepartmental Research Centre for Sexual Medicine (CIRMS), University of Naples, Federico II, Naples, Italy.
Roberta d'Emmanuele di Villa
Rd
Bianca
Emma
E
Mitidieri
Ferdinando
F
Fusco
Elena
E
D'Aiuto
Paolo
P
Grieco
Ettore
E
Novellino
Ciro
C
Imbimbo
Vincenzo
V
Mirone
Giuseppe
G
Cirino
Raffaella
R
Sorrentino
D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010410:Penile Erection; D014579:Urotensins / Q000502:physiology*
D014579:Urotensins; D009569:Nitric Oxide; C029677:urotensin II; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III