TRPV1 is involved in stretch-evoked contractile changes in the rat autonomous bladder model: A study with piperine, a new TRPV1 agonist
TRPV1 is involved in stretch-evoked contractile changes in the rat autonomous bladder model: A study with piperine, a new TRPV1 agonist
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DOI：
10.1002/nau.20343
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发表时间：
2007-01-01
影响因子：
2
通讯作者：
De Ridder, Dirk
中科院分区：
文献类型：
--
作者：
Gevaert, Thomas;Vandepitte, Joachim;De Ridder, Dirk
目的：辣椒素和树脂毒素（RTX）等香草素类药物已被用于治疗神经源性逼尿肌过度活动超过十年。最近，香草素分子胡椒碱（PIP）已被证明具有与这些药物相似的药理学性质。在这项研究中，我们观察了PIP对自主膀胱收缩活动的影响，特别感兴趣的是其对瞬时受体电位通道1（TRPV 1）受体的选择性。此外，我们使用选择性和非选择性TRPV 1拮抗剂研究了TRPV 1在容量诱导的收缩变化中的作用。方法：采用大鼠膀胱模型观察PIP的急性和长期作用。切除每个膀胱并置于加热的器官浴中，测量膀胱内压。在急性实验中，将PIP直接加入到浴液中。为了延长效应，用载体（5%乙醇）或PIP（10（-4）M）膀胱内预处理动物，并在72小时后处死。还研究了选择性（辣椒平（CZP））和非选择性（钌红（RR））TRPV 1拮抗剂对容积诱发收缩参数的影响。结果：PIP 10（-4）M急性给药可显著增加膀胱收缩幅度（p < 0.05）。TRPV 1选择性拮抗剂CZP（10（-5）M）和非选择性TRP拮抗剂RR（10（-5）M）可显著拮抗这些作用（p < 0.05）。与对照相比，用PIP进行膀胱内预处理诱导了更短的收缩和更多的非活动期（p < 0.05）。用CZP和RR抑制TRPV 1可显著降低容量诱发的离体膀胱收缩幅度的升高（p < 0.05）。结论：PIP对膀胱收缩力的急性和长期影响可能是通过TRPV 1介导的。此外，我们发现TRPV 1参与机械刺激的传入信号的证据。
Aim: Vanilloids like capsaicin and resiniferatoxin (RTX) have been used for more than a decade in the treatment of neurogenic detrusor overactivity. Recently, the vanilloid molecule piperine (PIP) has been shown to have similar pharmacological properties as these drugs. in this study, we looked at PIP-effects on autonomous bladder contractile activity, with particular interest for its selectivity for the transient receptor potential channel 1 (TRPV1) receptor. Additionally, we studied the role of TRPV1 in volume-induced contractile changes using selective and non-selective TRPV1 antagonists. Methods: The acute and prolonged effects of PIP were studied on rat bladders. Each bladder was excised and placed in a heated organ bath, where intravesical pressures were measured. in acute experiments, PIP was added directly to the bathing solution. For prolonged effects, animals were pretreated intravesically with vehicle (ethanol 5%) or PIP (10(-4) M) and sacrificed 72 hr later. The effects of selective (capsazepine (CZP)) and non-selective (ruthenium red (RR)) TRPV1 antagonists on volume-evoked contractile parameters were also studied. Results: Acute administration of PIP 10(-4) M significantly increased amplitude of bladder contractions (p < 0.05). These effects were significantly antagonized (p < 0.05) by the TRPV1-selective antagonist CZP (10(-5) M) and the non-selective TRP-antagonist RR (10(-5) M). Intravesical pre-treatment with PIP induced shorter contractions with more periods of non-activity (p < 0.05) compared to controls. Inhibition of TRPV1 with CZP and RR significantly reduced the volume-evoked rise in contractile amplitude in isolated bladders (p < 0.05). Conclusion: We found evidence for acute and prolonged effects of PIP on bladder contractility, which seem to be mediated through TRPV1. Furthermore, we found evidence for involvement of TRPV1 in afferent signaling of mechanical stimuli.