Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Peptides. 2009 Dec;30(12):2348-56. doi: 10.1016/j.peptides.2009.07.025. Epub 2009 Aug 8.
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.
本研究旨在探讨脊髓内源性阿片促黑素原（orexin-A）对正常大鼠和环磷酰胺（CYP）诱导膀胱炎模型膀胱功能的影响。在乌拉坦麻醉的正常和 CYP 诱导膀胱炎大鼠持续膀胱测压（CMG）期间，观察鞘内（i.t.）注射不同浓度 orexin-A（0.01、0.1 和 1.0 nmol）对膀胱功能的影响。观察鞘内注射选择性 orexin-1 受体（OXR1）拮抗剂 SB334867（10 nmol）对正常大鼠 orexin-A 诱导的膀胱过度活动以及 SB334867（10 和 30 nmol）对正常和 CYP 诱导膀胱炎大鼠膀胱功能变化的影响。还观察了静脉（i.v.）注射 orexin-A（0.3 和 1.0 nmol）对正常大鼠排尿反射的影响。鞘内注射 orexin-A（0.1 和 1.0 nmol）可显著缩短正常和 CYP 诱导膀胱炎大鼠的膀胱收缩间隔（ICI）。鞘内注射 SB334867（10 nmol）可显著增加正常大鼠 orexin-A 诱导的过度活跃膀胱的 ICI，鞘内注射 SB334867（30 nmol）也可增加正常大鼠膀胱的 ICI。然而，在 CYP 注射的膀胱炎大鼠模型中，鞘内注射 SB334867 并未改变膀胱功能。静脉注射 orexin-A 对正常大鼠膀胱功能没有影响。CYP 诱导膀胱炎大鼠下丘脑外侧区 orexin mRNA 水平显著降低。这些结果表明，脊髓内源性阿片促黑素原通过 OXR1 激活正常大鼠排尿反射。此外，OXR1 拮抗剂对 CYP 诱导膀胱炎大鼠的排尿反射没有影响。
