Involvement of orexin-A on micturition reflex in normal and cyclophosphamide-induced cystitis bladder in rat
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- 作者：Mizuki Kobayashi ; Masayoshi Nomura ; Hiroaki Fujihara ; Hitoshi Suzuki ; Hiroki Otsubo ; Hisae Nishii ; Naohiro Fujimoto ; Tetsuro Matsumoto ; Yoichi Ueta
- 关键词：Bladder ; Micturition reflex ; Orexin-A ; Orexin-1 receptor ; Spinal cord
- 刊名：Peptides
- 出版年：2009
- 出版时间：December 2009
- 年：2009
- 卷：30
- 期：12
- 页码：2348-2356
- 全文大小：526 K
文摘
The purpose of the present study was to investigate the effect of orexin-A in the spinal cord on bladder function in normal rats and cyclophosphamide (CYP)-induced cystitis rat models. The effects of intrathecal (i.t.) injection of orexin-A (0.01, 0.1 and 1.0 nmol) on bladder function were examined during continuous infusion cystometrogram (CMG) in urethane anesthetized normal and CYP-induced cystitis rats. The effects of i.t. injection of selective orexin-1 receptor (OXR1) antagonist SB334867 (10 nmol) on orexin-A-induced bladder overactivity in normal rats and SB334867 (10 and 30 nmol) on changes in bladder function in normal and CYP-induced cystitis rats were investigated. The effects of intravenous (i.v.) injection of orexin-A (0.3 and 1.0 nmol) on micturition reflex were also investigated in normal rats. I.t. injection of orexin-A (0.1 and 1.0 nmol) significantly decreased the intercontraction intervals (ICI) in normal and CYP-induced cystitis rats. I.t. injection of SB334867 (10 nmol) significantly increased the ICI of orexin-A induced overactive bladder in normal rats and i.t. injection of SB334867 (30 nmol) also increased the ICI in normal rat bladder. However, in CYP-injected cystitis rat models, i.t. injection of SB334867 did not change the bladder function. I.v. injection of orexin-A failed to affect the bladder function in normal rats. Orexin mRNA levels in the lateral hypothalamus were significantly decreased in CYP-induced cystitis rats. These results indicate that orexin-A in the spinal cord activates micturition reflex via OXR1 in normal rats. In addition, OXR1 antagonist did not have any effect on micturition reflex in CYP-induced cystitis rats.