Urotensin-II （U-II） is a cyclic peptide that acts through a G protein-coupled receptor （urotensin-II receptor [UTR]） mainly involved in cardiovascular function in humans. The urotensinergic system is also implicat...Urotensin-II （U-II） is a cyclic peptide that acts through a G protein-coupled receptor （urotensin-II receptor [UTR]） mainly involved in cardiovascular function in humans. The urotensinergic system is also implicated in the urogenital tract. Indeed, U-II relaxes human corpus cavernosum strips and causes an increase in intracavernous pressure （ICP） in rats. In light of this, the U-II/UTR pathway can be considered a new target for the treatment of erectile dysfunction. On this hypothesis, herein we report on two new UTR high affinity-agonists, P5U （H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH） and UPG84（H-Asp-c[Pen-Phe-DTrp-Orn-（pNH2） Phe-Cys]-Val-OH）. The effects of P5U and UPG84 were each compared separately with U-II by monitoring the ICP in anesthetized rats. Intracavernous injection of U-II （0.03-1 nmol）, P5U （0.03-1 nmol） or UPG84 （0.03-1 nmol） caused an increase in ICP. P5U, in particular, elicited a significant increase in ICP as compared to U-II. The observed effect by using P5U at a dose of 0.1 nmol per rat was comparable to the effect elicited by U-II at a dose of 0.3 nmol. Moreover, UPG84 at the lowest dose （0.03 nmol） showed an effect similar to the highest dose of U-II （1 nmol）. Furthermore, UPG84 was found to be more effective than P5U. Indeed, while the lowest dose of P5U （0.03 nmol） did not affect the ICP, UPG84, at the same dose, induced a prominent penile erection in rat. These compounds did not modify the blood pressure, which indicates a good safety profile. In conclusion, UPG84 and P5U may open new perspectives for the management of erectile dysfunction.展开更多
文摘Urotensin-II （U-II） is a cyclic peptide that acts through a G protein-coupled receptor （urotensin-II receptor [UTR]） mainly involved in cardiovascular function in humans. The urotensinergic system is also implicated in the urogenital tract. Indeed, U-II relaxes human corpus cavernosum strips and causes an increase in intracavernous pressure （ICP） in rats. In light of this, the U-II/UTR pathway can be considered a new target for the treatment of erectile dysfunction. On this hypothesis, herein we report on two new UTR high affinity-agonists, P5U （H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH） and UPG84（H-Asp-c[Pen-Phe-DTrp-Orn-（pNH2） Phe-Cys]-Val-OH）. The effects of P5U and UPG84 were each compared separately with U-II by monitoring the ICP in anesthetized rats. Intracavernous injection of U-II （0.03-1 nmol）, P5U （0.03-1 nmol） or UPG84 （0.03-1 nmol） caused an increase in ICP. P5U, in particular, elicited a significant increase in ICP as compared to U-II. The observed effect by using P5U at a dose of 0.1 nmol per rat was comparable to the effect elicited by U-II at a dose of 0.3 nmol. Moreover, UPG84 at the lowest dose （0.03 nmol） showed an effect similar to the highest dose of U-II （1 nmol）. Furthermore, UPG84 was found to be more effective than P5U. Indeed, while the lowest dose of P5U （0.03 nmol） did not affect the ICP, UPG84, at the same dose, induced a prominent penile erection in rat. These compounds did not modify the blood pressure, which indicates a good safety profile. In conclusion, UPG84 and P5U may open new perspectives for the management of erectile dysfunction.
