Spinal CRH facilitates the micturition reflex via the CRH2 receptor in rats with normal bladder and bladder outlet obstruction
Abstract Lower urinary tract symptoms (LUTS) significantly affect patient quality of life. Treatment options for bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) (a common cause of LUTS) are insufficient to relieve discomfort. As the incidence of BPH is increasing, new phar...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-87990-w |
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| author | Risa Shinoki Ryosuke Jikuya Takuma Nirei Takeshi Fukazawa Hiroki Takizawa Mari Hioki Sachi Kawaura Tomoyuki Tatenuma Go Noguchi Daiki Ueno Yusuke Ito Mitsuru Komeya Kentaro Muraoka Hisashi Hasumi Kazuki Kobayashi Masahito Takiguchi Kengo Funakoshi Kazuhide Makiyama Naoki Aizawa Hiroki Ito |
| author_facet | Risa Shinoki Ryosuke Jikuya Takuma Nirei Takeshi Fukazawa Hiroki Takizawa Mari Hioki Sachi Kawaura Tomoyuki Tatenuma Go Noguchi Daiki Ueno Yusuke Ito Mitsuru Komeya Kentaro Muraoka Hisashi Hasumi Kazuki Kobayashi Masahito Takiguchi Kengo Funakoshi Kazuhide Makiyama Naoki Aizawa Hiroki Ito |
| author_sort | Risa Shinoki |
| collection | DOAJ |
| description | Abstract Lower urinary tract symptoms (LUTS) significantly affect patient quality of life. Treatment options for bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) (a common cause of LUTS) are insufficient to relieve discomfort. As the incidence of BPH is increasing, new pharmacological targets for LUTS treatment are required. Corticotropin-releasing hormone (CRH) is a neuropeptide that controls normal micturition in rodents. Herein, we investigated the role of spinal CRH in regulating micturition in sham and BOO rats, and evaluated CRH as a therapeutic target for bladder dysfunction in BOO model Sprague–Dawley rats. Histological analysis, cystometry with intrathecal administration of CRH agonists/antagonists, western blotting, and real-time PCR assessed the role of CRH and its receptors (CRHR1 and CRHR2) in micturition in sham and BOO rats. CRH administration shortened the voiding interval, while pretreatment with antagonists against CRHR2 (but not CRHR1) suppressed CRH-induced frequent voiding. Western blotting confirmed CRHR1 expression in the dorsal root ganglia (DRG) and bladder, but not the spinal cord, of rats. Real-time PCR showed higher CRHR2 mRNA expression in the spinal cord and DRG than in the bladder in both groups. Overall, spinal CRH facilitates the micturition reflex via CRHR2, and is a promising therapeutic target for LUTS. |
| format | Article |
| id | doaj-art-bc0b14bfb7ad432bb0cdd697520f880b |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-bc0b14bfb7ad432bb0cdd697520f880b2025-02-02T12:23:55ZengNature PortfolioScientific Reports2045-23222025-01-011511910.1038/s41598-025-87990-wSpinal CRH facilitates the micturition reflex via the CRH2 receptor in rats with normal bladder and bladder outlet obstructionRisa Shinoki0Ryosuke Jikuya1Takuma Nirei2Takeshi Fukazawa3Hiroki Takizawa4Mari Hioki5Sachi Kawaura6Tomoyuki Tatenuma7Go Noguchi8Daiki Ueno9Yusuke Ito10Mitsuru Komeya11Kentaro Muraoka12Hisashi Hasumi13Kazuki Kobayashi14Masahito Takiguchi15Kengo Funakoshi16Kazuhide Makiyama17Naoki Aizawa18Hiroki Ito19Department of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokosuka Kyosai HospitalDepartment of Neuroanatomy, Yokohama City University Graduate School of MedicineDepartment of Neuroanatomy, Yokohama City University Graduate School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineDepartment of Pharmacology and Toxicology, Dokkyo Medical University School of MedicineDepartment of Urology, Yokohama City University Graduate School of MedicineAbstract Lower urinary tract symptoms (LUTS) significantly affect patient quality of life. Treatment options for bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) (a common cause of LUTS) are insufficient to relieve discomfort. As the incidence of BPH is increasing, new pharmacological targets for LUTS treatment are required. Corticotropin-releasing hormone (CRH) is a neuropeptide that controls normal micturition in rodents. Herein, we investigated the role of spinal CRH in regulating micturition in sham and BOO rats, and evaluated CRH as a therapeutic target for bladder dysfunction in BOO model Sprague–Dawley rats. Histological analysis, cystometry with intrathecal administration of CRH agonists/antagonists, western blotting, and real-time PCR assessed the role of CRH and its receptors (CRHR1 and CRHR2) in micturition in sham and BOO rats. CRH administration shortened the voiding interval, while pretreatment with antagonists against CRHR2 (but not CRHR1) suppressed CRH-induced frequent voiding. Western blotting confirmed CRHR1 expression in the dorsal root ganglia (DRG) and bladder, but not the spinal cord, of rats. Real-time PCR showed higher CRHR2 mRNA expression in the spinal cord and DRG than in the bladder in both groups. Overall, spinal CRH facilitates the micturition reflex via CRHR2, and is a promising therapeutic target for LUTS.https://doi.org/10.1038/s41598-025-87990-wBladder outlet obstructionCorticotropin-releasing hormoneLower urinary tract symptomsBenign prostatic hyperplasia |
| spellingShingle | Risa Shinoki Ryosuke Jikuya Takuma Nirei Takeshi Fukazawa Hiroki Takizawa Mari Hioki Sachi Kawaura Tomoyuki Tatenuma Go Noguchi Daiki Ueno Yusuke Ito Mitsuru Komeya Kentaro Muraoka Hisashi Hasumi Kazuki Kobayashi Masahito Takiguchi Kengo Funakoshi Kazuhide Makiyama Naoki Aizawa Hiroki Ito Spinal CRH facilitates the micturition reflex via the CRH2 receptor in rats with normal bladder and bladder outlet obstruction Scientific Reports Bladder outlet obstruction Corticotropin-releasing hormone Lower urinary tract symptoms Benign prostatic hyperplasia |
| title | Spinal CRH facilitates the micturition reflex via the CRH2 receptor in rats with normal bladder and bladder outlet obstruction |
| title_full | Spinal CRH facilitates the micturition reflex via the CRH2 receptor in rats with normal bladder and bladder outlet obstruction |
| title_fullStr | Spinal CRH facilitates the micturition reflex via the CRH2 receptor in rats with normal bladder and bladder outlet obstruction |
| title_full_unstemmed | Spinal CRH facilitates the micturition reflex via the CRH2 receptor in rats with normal bladder and bladder outlet obstruction |
| title_short | Spinal CRH facilitates the micturition reflex via the CRH2 receptor in rats with normal bladder and bladder outlet obstruction |
| title_sort | spinal crh facilitates the micturition reflex via the crh2 receptor in rats with normal bladder and bladder outlet obstruction |
| topic | Bladder outlet obstruction Corticotropin-releasing hormone Lower urinary tract symptoms Benign prostatic hyperplasia |
| url | https://doi.org/10.1038/s41598-025-87990-w |
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