Reduced bladder responses to capsaicin and GSK-1016790A in retired-breeder female rats with diminished volume sensitivity.
Reduced bladder responses to capsaicin and GSK-1016790A in retired-breeder female rats with diminished volume sensitivity.
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DOI：
10.1152/ajprenal.00198.2018
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发表时间：
2018-11
期刊：
影响因子：
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通讯作者：
Jiliang Wen;Shulu Zu;Zhenghao Chen;S. Daugherty;W. D. de Groat;Yuqiang Liu;Mingzhen Yuan;Guanghui Chen
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文献类型：
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作者：
Jiliang Wen;Shulu Zu;Zhenghao Chen;S. Daugherty;W. D. de Groat;Yuqiang Liu;Mingzhen Yuan;Guanghui Chen
文献记录了与年龄相关的膀胱感觉功能降低。瞬时受体电位香草酸（TRPV）1或TRPV 4通道已经涉及膀胱机械转导。为了研究TRPV 1或TRPV 4对年龄相关的膀胱感觉功能降低的贡献，使用多种方法比较了退休饲养员（RB; 12-15月龄）和年轻成年（2-3月龄）雌性大鼠对辣椒素（CAP; TRPV 1激动剂）和GSK-1016790 A（GSK; TRPV 4激动剂）的膀胱反应。代谢笼和连续输注膀胱测压[膀胱测压图（CMG）]记录显示，RB大鼠表现出更大的膀胱容量和更低的排尿频率。RB大鼠也有更大的膀胱内压力阈值排尿，但排尿收缩强度相当于年轻大鼠。膀胱内给予CAP（1 μM）或GSK（20 nM）在RB大鼠中引起的所有CMG参数变化较小。在体外，CAP（1 μM）或GSK（20 nM）引起的膀胱条收缩增强较小，而毒蕈碱受体激动剂卡巴胆碱（100、300和1，000 nM）引起RB大鼠更大幅度的收缩。膜片钳记录显示较小的CAP（100 nM）诱导的膀胱初级感觉神经元的内向电流，和Ca 2+成像显示较小的GSK（20 nM）诱发的RB大鼠尿路上皮细胞内Ca 2+浓度的增加。这些结果表明，RB大鼠具有老年女性常见的膀胱感觉功能下降，可以用作研究其机制的动物模型。膀胱传入神经中TRPV 1功能表达减少或尿路上皮TRPV 4功能表达减少可能与感觉功能减弱有关。
Literature documents an age-related reduction of bladder sensory function. Transient receptor potential vanilloid (TRPV)1 or TRPV4 channels have been implicated in bladder mechanotransduction. To investigate contributions of TRPV1 or TRPV4 to the age-related reduction of bladder sensory function, bladder responses to capsaicin (CAP; TRPV1 agonist) and GSK-1016790A (GSK; TRPV4 agonist) in retired breeder (RB; 12-15 mo) and young adult (2-3 mo) female rats were compared using multiple methods. Metabolic cage and continuous infusion cystometry [cystometrogram (CMG)] recordings revealed that RB rats exhibit larger bladder capacity and lower voiding frequency. RB rats also have a greater intravesical pressure threshold for micturition; however, the voiding contraction strength was equivalent to that in young rats. CAP (1 μM) or GSK (20 nM) administered intravesically evoked smaller changes in all CMG parameters in RB rats. In vitro, CAP (1 μM) or GSK (20 nM) evoked smaller enhancement of bladder strip contractions, while the muscarinic receptor agonist carbachol (at 100, 300, and 1,000 nM) elicited greater amplitude contractions in RB rats. Patch-clamp recording revealed smaller CAP (100 nM) induced inward currents in bladder primary sensory neurons, and Ca2+ imaging revealed smaller GSK (20 nM) evoked increases in intracellular Ca2+ concentration in urothelial cells in RB rats. These results suggest that RB rats have a decreased bladder sensory function commonly observed in elderly women, and could be used as an animal model to study the underling mechanisms. Reduced functional expression of TRPV1 in bladder afferents or reduced functional expression of urothelial TRPV4 may be associated with the diminished sensory function.