Department of Urology, Ludwig-Maximilians University Hospital, Munich, Germany.
J Urol. 2010 May;183(5):2070-6. doi: 10.1016/j.juro.2009.12.093. Epub 2010 Mar 19.
We studied whether TRPA1 agonists interact with sensory and inflammatory signals to relax human urethral smooth muscle.
Urethral specimens were obtained perioperatively from 19 patients, and prepared for immunohistochemistry and functional experiments. The effects of allyl isothiocyanate, cinnamaldehyde and NaHS were studied in phenylephrine activated preparations combined with capsaicin, capsazepine, N omega-nitro-L-arginine, indomethacin or CP55940.
TRPA1, cannabinoid 1 and cannabinoid 2 immunoreactivity was colocalized in nerve fibers of the human urethra. All TRPA1 agonists produced relaxation of phenylephrine contracted urethral preparations. Capsaicin increased relaxant responses to all TRPA1 agonists. It increased the mean +/- SEM -logIC50 of cinnamaldehyde and NaHS from 4.91 +/- 0.26 to 5.15 +/- 0.22 and 3.27 +/- 0.14 to 3.79 +/- 0.35, and the -logIC30 of allyl isothiocyanate from 3.11 +/- 0.24 to 3.41 +/- 0.26 (each p <0.05). Capsazepine in 5 preparations, indomethacin in 6 and CP55940 in 5 decreased cinnamaldehyde mediated relaxation by up to 39%, 88% and 89%, respectively. Nomega-nitro-L-arginine and urothelial removal had no effect on relaxation by cinnamaldehyde in 5 preparations.
Relaxation to TRPA1 agonists in human urethral preparations seem to work in cooperation with TRPV1 mediated signals, are negatively coupled via cannabinoid receptor activation and involve cyclooxygenase products. Urothelial TRPA1 signals may not be important to regulate normal human urethral smooth muscle tone. This does not exclude a role in the initiation of afferent activity normally and in disease states.
我们研究了瞬时受体电位通道 A1（TRPA1）激动剂是否与感觉和炎症信号相互作用，从而舒张人尿道平滑肌。
手术期间从 19 名患者中获得尿道标本，并进行免疫组织化学和功能实验。在苯肾上腺素激活的标本中研究丙烯基异硫氰酸酯、肉桂醛和 NaHS 的作用，同时加入辣椒素、辣椒平、Nω-硝基-L-精氨酸、吲哚美辛或 CP55940。
TRPA1、大麻素 1 和大麻素 2 免疫反应性在人尿道神经纤维中存在共定位。所有 TRPA1 激动剂均可舒张苯肾上腺素收缩的尿道标本。辣椒素增加了所有 TRPA1 激动剂的舒张反应。它使肉桂醛和 NaHS 的平均-对数 IC50 分别从 4.91±0.26 增加到 5.15±0.22 和 3.27±0.14 增加到 3.79±0.35，丙烯基异硫氰酸酯的-对数 IC30 从 3.11±0.24 增加到 3.41±0.26（p<0.05）。在 5 个标本中，辣椒平在 6 个标本中，CP55940 在 5 个标本中，肉桂醛介导的舒张作用分别减少了 39%、88%和 89%。Nω-硝基-L-精氨酸和尿路上皮去除对 5 个标本中肉桂醛的舒张作用没有影响。
人尿道标本中对 TRPA1 激动剂的舒张作用似乎与 TRPV1 介导的信号协同作用，通过大麻素受体激活负偶联，并涉及环氧化酶产物。尿路上皮的 TRPA1 信号可能对调节正常人类尿道平滑肌张力不重要。这并不排除在正常和疾病状态下对传入活动的起始的作用。
