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TRPV1 通道在下尿路酸性刺激中的功能作用:去大脑非麻醉小鼠雌雄差异的体内评估。

Functional roles of TRPV1 channels in lower urinary tract irritated by acetic acid: in vivo evaluations of the sex difference in decerebrate unanesthetized mice.

机构信息

Department of Urology, University of Yamanashi Interdisciplinary Graduate School of Medicine and Engineering, Chuo, Yamanashi, Japan.

出版信息

Am J Physiol Renal Physiol. 2010 Jun;298(6):F1351-9. doi: 10.1152/ajprenal.00695.2009. Epub 2010 Mar 17.

Abstract

Sex-specific differences in activity of the lower urinary tract (LUT) responding to acid irritation in mice have been revealed. This study, using continuous infusion cystometry with acetic acid (AA; pH 3.0), was conducted to examine whether the transient receptor potential vanilloid type 1 (TRPV1) channels expressed in the mouse LUT are involved in the sex difference in functional responses of the bladder and urethra to irritation. No differences were found between effects of capsazepine (a TRPV1 blocker; 100 microM) and those of its vehicle on any of the cystometric changes by intravesical AA in either female or male mice. However, capsazepine eliminated the acid-induced sex differences in parameters associated with bladder contraction phase (i.e., maximal voiding pressure, closing peak pressure, 2nd-phase contraction, bladder contraction duration), whereas capsazepine did not affect those in parameters associated with bladder-filling period (i.e., intercontraction interval, actual collecting time). In males, capsazepine reduced the number of bladder contractions accompanying fluid dribbling at 2nd-phase contraction, which is indicative of the urethral response to irritation, whereas in females it increased the number. Together, these results suggest the possibilities that TRPV1 channels in the bladder and urethra are involved in the sex difference in the LUT response to acid irritation and that these participate, e.g., via "cross talk" between the bladder and urethra, in the fine-tuning of intravesical pressure (or bladder emptying) at the bladder contraction phase under irritated LUT conditions but not in sensing for bladder filling during the storage period, although the contribution of the mechanism may be small.

摘要

已揭示出小鼠下尿路(LUT)对酸刺激的活性存在性别特异性差异。本研究使用乙酸(AA;pH 3.0)持续输注膀胱测压法,旨在研究在膀胱和尿道对刺激的功能反应中存在性别差异的情况下,LUT 中表达的瞬时受体电位香草酸型 1(TRPV1)通道是否参与其中。在雌性或雄性小鼠的膀胱内 AA 作用下,辣椒素(TRPV1 阻滞剂;100 μM)及其载体对任何膀胱测压变化的影响均无差异。然而,辣椒素消除了与膀胱收缩期相关的参数的酸诱导性别差异(即最大排空压力、关闭峰值压力、第 2 相收缩、膀胱收缩持续时间),而辣椒素不影响与膀胱充盈期相关的参数(即收缩间期、实际收集时间)。在雄性中,辣椒素减少了伴随第 2 相收缩出现的尿滴伴随的膀胱收缩次数,这表明尿道对刺激的反应,而在雌性中则增加了收缩次数。总之,这些结果表明,膀胱和尿道中的 TRPV1 通道可能参与了 LUT 对酸刺激的性别差异反应,并且这些通道可能通过“膀胱和尿道之间的串扰”参与了在受刺激的 LUT 条件下膀胱收缩期的膀胱内压力(或膀胱排空)的精细调节,但在存储期间不参与膀胱充盈的感觉,尽管该机制的贡献可能很小。

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