The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats
Objective: This study aimed to investigate the effects of treatment with palosuran, a urotensin receptor blocker, on molecular changes in the corpora cavernosa (CC) in diabetic rats. Methods: Streptozotocin-induced diabetic rats were treated with palosuran 300 mg/kg per day for 6 weeks. Contraction...
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Elsevier
2025-01-01
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| Series: | Asian Journal of Urology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214388224000560 |
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| author | Murat Olukman Cenk Can Sibel Ülker Yiğit Uyanikgil Türker Çavuşoğlu Neslihan Düzenli Deniz Coşkunsever Fatma G. Kozcu |
| author_facet | Murat Olukman Cenk Can Sibel Ülker Yiğit Uyanikgil Türker Çavuşoğlu Neslihan Düzenli Deniz Coşkunsever Fatma G. Kozcu |
| author_sort | Murat Olukman |
| collection | DOAJ |
| description | Objective: This study aimed to investigate the effects of treatment with palosuran, a urotensin receptor blocker, on molecular changes in the corpora cavernosa (CC) in diabetic rats. Methods: Streptozotocin-induced diabetic rats were treated with palosuran 300 mg/kg per day for 6 weeks. Contraction of CC induced by potassium chloride, phenylephrine, and NG-nitro-L-arginine methyl ester and relaxation of CC induced by electrical field stimulation (EFS) and sodium nitroprusside (SNP) (endothelium-dependent and endothelium-independent stimuli, respectively), and Y-27632 (Rho-kinase inhibitor) were examined in organ baths. Direct contraction or relaxation induced by palosuran and urotensin-II (U-II) were also evaluated. The expression levels of nitric oxide synthetases (NOSs), RhoA, oxidative stress regulators, and U-II were analyzed by Western blotting or immunohistochemistry. Results: Induction of diabetes in rats resulted in the decreased relaxant response to SNP, decreased pD2 value of SNP, attenuated relaxant response to Y-27632 as well as the decreased RhoA expression in CC. Palosuran treatment of diabetic rats reversed all of these parameters; however, it further impaired the already weakened relaxation of diabetic CC in response to EFS. Although induction of diabetes did not change U-II expression in CC significantly, palosuran treatment reduced U-II expression in diabetic CC. The expression level of nNOS was lowered in diabetic CC; however, palosuran treatment did not change the decreased the neuronal NOS expression. In vitro exposure of diabetic CC strips to palosuran produced a direct relaxant response. Conclusion: Palosuran treatment did not affect the expression of NOSs or reduce nitrergic conduction induced by EFS stimulation in diabetic CC. However, while directly triggering a relaxant response, it did not induce a prominent contraction either by decreasing U-II expression, or increasing the sensitivity of CC to nitric oxide which suggested that palosuran has the potential to support erectile function. Further and comprehensive studies are required to clarify this issue. |
| format | Article |
| id | doaj-art-b86941067bf7467a943537bcbb2c18f2 |
| institution | Kabale University |
| issn | 2214-3882 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Asian Journal of Urology |
| spelling | doaj-art-b86941067bf7467a943537bcbb2c18f22025-01-30T05:14:16ZengElsevierAsian Journal of Urology2214-38822025-01-01121116126The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic ratsMurat Olukman0Cenk Can1Sibel Ülker2Yiğit Uyanikgil3Türker Çavuşoğlu4Neslihan Düzenli5Deniz Coşkunsever6Fatma G. Kozcu7Department of Medical Pharmacology, Faculty of Medicine, Ege University, Izmir, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine, Ege University, Izmir, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine, Ege University, Izmir, TurkeyDepartment of Histology and Embryology, Cord Blood, Cell-Tissue Application and Research Center, Faculty of Medicine, Ege University, Izmir, TurkeyDepartment of Histology and Embryology, Cord Blood, Cell-Tissue Application and Research Center, Faculty of Medicine, Ege University, Izmir, Turkey; Department of Histology and Embryology, Faculty of Medicine, Izmir Bakırcay University, Izmir, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine, Ege University, Izmir, Turkey; Department of Medical Pharmacology, Faculty of Medicine, İzmir Democracy University, Izmir, Turkey; Corresponding author. Department of Medical Pharmacology, Faculty of Medicine, İzmir Democracy University, Izmir, Turkey.Department of Medical Pharmacology, Faculty of Medicine, Ege University, Izmir, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine, Ege University, Izmir, TurkeyObjective: This study aimed to investigate the effects of treatment with palosuran, a urotensin receptor blocker, on molecular changes in the corpora cavernosa (CC) in diabetic rats. Methods: Streptozotocin-induced diabetic rats were treated with palosuran 300 mg/kg per day for 6 weeks. Contraction of CC induced by potassium chloride, phenylephrine, and NG-nitro-L-arginine methyl ester and relaxation of CC induced by electrical field stimulation (EFS) and sodium nitroprusside (SNP) (endothelium-dependent and endothelium-independent stimuli, respectively), and Y-27632 (Rho-kinase inhibitor) were examined in organ baths. Direct contraction or relaxation induced by palosuran and urotensin-II (U-II) were also evaluated. The expression levels of nitric oxide synthetases (NOSs), RhoA, oxidative stress regulators, and U-II were analyzed by Western blotting or immunohistochemistry. Results: Induction of diabetes in rats resulted in the decreased relaxant response to SNP, decreased pD2 value of SNP, attenuated relaxant response to Y-27632 as well as the decreased RhoA expression in CC. Palosuran treatment of diabetic rats reversed all of these parameters; however, it further impaired the already weakened relaxation of diabetic CC in response to EFS. Although induction of diabetes did not change U-II expression in CC significantly, palosuran treatment reduced U-II expression in diabetic CC. The expression level of nNOS was lowered in diabetic CC; however, palosuran treatment did not change the decreased the neuronal NOS expression. In vitro exposure of diabetic CC strips to palosuran produced a direct relaxant response. Conclusion: Palosuran treatment did not affect the expression of NOSs or reduce nitrergic conduction induced by EFS stimulation in diabetic CC. However, while directly triggering a relaxant response, it did not induce a prominent contraction either by decreasing U-II expression, or increasing the sensitivity of CC to nitric oxide which suggested that palosuran has the potential to support erectile function. Further and comprehensive studies are required to clarify this issue.http://www.sciencedirect.com/science/article/pii/S2214388224000560Corpora cavernosaDiabetes mellitusExperimentalErectile dysfunctionNitric oxidePalosuran |
| spellingShingle | Murat Olukman Cenk Can Sibel Ülker Yiğit Uyanikgil Türker Çavuşoğlu Neslihan Düzenli Deniz Coşkunsever Fatma G. Kozcu The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats Asian Journal of Urology Corpora cavernosa Diabetes mellitus Experimental Erectile dysfunction Nitric oxide Palosuran |
| title | The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats |
| title_full | The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats |
| title_fullStr | The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats |
| title_full_unstemmed | The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats |
| title_short | The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats |
| title_sort | effects of the urotensin ii receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin induced diabetic rats |
| topic | Corpora cavernosa Diabetes mellitus Experimental Erectile dysfunction Nitric oxide Palosuran |
| url | http://www.sciencedirect.com/science/article/pii/S2214388224000560 |
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