Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1

被引:525
作者
Birder, LA [1 ]
Nakamura, Y
Kiss, S
Nealen, ML
Barrick, S
Kanai, AJ
Wang, E
Ruiz, G
de Groat, WC
Apodaca, G
Watkins, S
Caterina, MJ
机构
[1] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div,Lab Epithelial Cell Biol, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15213 USA
[4] Kanazawa Univ, Sch Med, Dept Urol, Kanazawa, Ishikawa 9208641, Japan
[5] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA
[6] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
关键词
D O I
10.1038/nn902
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the urinary bladder, the capsaicin-gated ion channel TRPV1 is expressed both within afferent nerve terminals and within the epithelial cells that line the bladder lumen. To determine the significance of this expression pattern, we analyzed bladder function in mice lacking TRPV1. Compared with wild-type littermates, trpv1(-/-) mice had a higher frequency of low-amplitude, nonvoiding bladder contractions. This alteration was accompanied by reductions in both spinal cord signaling and reflex voiding during bladder filling (under anesthesia). In vitro, stretch-evoked ATP release and membrane capacitance changes were diminished in bladders excised from trpv1(-/-) mice, as was hypoosmolality-evoked ATP release from cultured trpv1(-/-) urothelial cells. These findings indicate that TRPV1 participates in normal bladder function and is essential for normal mechanically evoked purinergic signaling by the urothelium.
引用
收藏
页码:856 / 860
页数:5
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