Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder
Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder
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DOI：
10.1016/j.eururo.2007.10.024
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发表时间：
2008-02-01
期刊：
影响因子：
23.4
通讯作者：
Zygmunt, Peter M.
中科院分区：
文献类型：
--
作者：
Streng, Tomi;Axelsson, Helena E.;Zygmunt, Peter M.
目的：研究瞬时受体电位(Trp)A1离子通道在大鼠膀胱中的分布，以及硫化氢(H 2S)和已知的TRPA1激动剂对清醒大鼠排尿的影响以及对异源表达离子通道的影响。对清醒动物进行了膀胱内注射硫化氢钠(NaHS，硫化氢供体)、异硫氰酸烯丙酯(AI)和肉桂醛(CA)的膀胱计量学研究。结果：尿路上皮、上皮下间隙、肌层及膀胱血管周围的无髓神经纤维均有TRPA1免疫反应阳性。所有TRPA1免疫反应神经纤维也表达TRPV1免疫反应，反之亦然。TRPA1在尿路上皮细胞中也在转录和蛋白水平上被检测到。AI可增加排尿频率，减少排尿量。在用硫酸鱼精蛋白破坏尿路上皮屏障后，CA和NaHS的尿动力学参数发生了类似的变化。结论：TRPA1在膀胱C纤维传入细胞和尿路上皮细胞上的表达，以及膀胱内TRPA1激动剂引起逼尿肌过度活动的研究表明，TRPA1可能在该器官的感觉传导中起作用。这项研究还强调，硫化氢是一种TRPA1激活剂，可能与炎症性膀胱病有关。(C)2007年，爱思唯尔公司代表欧洲泌尿学协会出版。
Objectives: To investigate the distribution of the transient receptor potential (TRP) A1 ion channel in the rat urinary bladder, and to study the effects of hydrogen sulfide (H2S) and known TRPA1 activators on micturition in conscious rats and on heterologously expressed ion channels.Methods: The expression of TRPA1 in urinary bladder was studied with fluorescence immunohistochemistry and real-time PCR in female Sprague-Dawley rats. Cystometric investigations were performed in conscious animals subjected to intravesical administration of sodium hydrogen sulfide (NaHS, donor of H2S), allyl isothiocyanate (AI), and cinnamaldehyde (CA). Fluorometric calcium imaging was used to study the effect of NaHS on human and mouse TRPA1 expressed in CHO cells.Results: TRPA1 immunoreactivity was found on unmyelinated nerve fibres within the urothelium, suburothelial space, and muscle layer as well as around blood vessels throughout the bladder. All TRPA1 immunoreactive nerves fibres also expressed TRPV1 immunoreactivity and vice versa. TRPA1 was also detected in urothelial cells at both transcriptional and protein levels. AI increased micturition frequency and reduced voiding volume. CA and NaHS produced similar changes in urodynamic parameters after disruption of the urothelial barrier with protamine sulfate. NaHS also induced calcium responses in TRPA1-expressing CHO cells, but not in untransfected cells.Conclusions: The expression of TRPA1 on C-fibre bladder afferents and urothelial cells together with the finding that intravesical TRPA1 activators initiate detrusor overactivity indicate that TRPA1 may have a role in sensory transduction in this organ. The study also highlights H2S as a TRPA1 activator potentially involved in inflammatory bladder disease. (c) 2007 Published by Elsevier B.V. on behalf of European Association of Urology.