Region-specific changes in the phosphorylation of ERK1/2 and ERK5 in rat micturition pathways following cyclophosphamide-induced cystitis
Region-specific changes in the phosphorylation of ERK1/2 and ERK5 in rat micturition pathways following cyclophosphamide-induced cystitis
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DOI：
10.1152/ajpregu.00570.2006
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发表时间：
2007-03-01
影响因子：
2.8
通讯作者：
Gulick, Melisa A.
中科院分区：
文献类型：
--
作者：
Qiao, Li-Ya;Gulick, Melisa A.
膀胱的慢性炎症产生痛觉过敏和异常性疼痛。越来越多的证据表明ERK在介导躯体和内脏疼痛处理中的作用。在目前的研究中，我们的特点和比较激活的两个ERK亚型，ERK 1/2和ERK 5，在排尿途径，包括膀胱，腰骶背根神经节（DRG），脊髓在成年雌性和雄性大鼠之前和之后环磷酰胺（环磷酰胺）诱导的膀胱炎症。结果显示，膀胱炎后这些区域的ERK 1/2和ERK 5的差异激活。与对照组相比，膀胱组织中磷酸化ERK 1/2水平升高，磷酸化ERK 5水平未升高;背根节中磷酸化ERK 5水平升高，磷酸化ERK 1/2水平未升高;腰髓中磷酸化ERK 1/2水平升高，磷酸化ERK 5水平未升高。膀胱炎诱导的磷酸化ERK 1/2和磷酸化ERK 5的上调具有时间依赖性，并且在雌性和雄性大鼠中显示出相似的模式。膀胱组织磷酸化ERK 1/2水平在注药后2、8 h升高，背根节磷酸化ERK 5水平在注药后8、48 h升高，腰髓磷酸化ERK 1/2水平在注药后48 h升高。磷酸化ERK 5仅在DRG神经元中增加，而磷酸化ERK 1/2在膀胱炎后脊髓和膀胱中增加，这一结果表明神经营养因子对膀胱炎症后排尿途径的区域特异性作用。
Chronic inflammation of the urinary bladder generates hyperalgesia and allodynia. Growing evidence suggests a role of ERK in mediating somatic and visceral pain processing. In the present studies, we characterized and compared the activation of two ERK isoforms, ERK1/2 and ERK5, in micturition pathways, including the urinary bladder, lumbosacral dorsal root ganglia (DRG), and spinal cord in adult female and male rats before and after cyclophosphamide (CYP)-induced bladder inflammation. Results showed differential activation of ERK1/2 and ERK5 in these regions following cystitis. The level of phospho-ERK1/2 but not phospho-ERK5 was increased in the urinary bladder; the level of phospho-ERK5 but not phospho-ERK1/2 was increased in DRG; and the level of phospho-ERK1/2 but not phospho-ERK5 was increased in lumbar spinal cord following cystitis compared with control. Cystitis-induced upregulation of phospho-ERK1/2 and phospho-ERK5 was time dependent and showed similar patterns in female and male rats. The level of phospho-ERK1/2 in bladder was increased at 2 and 8 h after CYP injection; the level of phospho-ERK5 in DRG was increased at 8 and 48 h after CYP injection; and the level of phospho-ERK1/2 in lumbar spinal cord was increased at 48 h after CYP injection. The result that phospho-ERK5 was exclusively increased in DRG neurons, while phospho-ERK1/2 was increased in the spinal cord and the urinary bladder after cystitis, suggests a region-specific effect of neurotrophins on micturition pathways following bladder inflammation.