Activation of bitter taste receptors (tas2rs) relaxes detrusor smooth muscle and suppresses overactive bladder symptoms.
Activation of bitter taste receptors (tas2rs) relaxes detrusor smooth muscle and suppresses overactive bladder symptoms.
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苦味受体 (tas2rs) 的激活可放松逼尿肌平滑肌并抑制膀胱过度活动症症状。
DOI：
10.18632/oncotarget.8549
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发表时间：
2016-04-19
期刊：
影响因子：
--
通讯作者：
Ji G
中科院分区：
文献类型：
--
作者：
Zhai K;Yang Z;Zhu X;Nyirimigabo E;Mi Y;Wang Y;Liu Q;Man L;Wu S;Jin J;Ji G
传统上认为苦味感受器（TAS2Rs）只在舌头的味蕾上表达。然而，越来越多的证据表明，除了味觉之外，这个受体家族在口腔外还具有非味觉功能。在这里，我们研究了TAS2Rs在人和小鼠逼尿肌平滑肌（DSM）中的作用。我们发现各种TAS2R亚型的mRNA在人和小鼠逼尿肌平滑肌（DSM）中都有不同水平的表达。氯喹（CLQ）是一种TAS2Rs激动剂，浓度依赖性地放松了乙醇和氯化钾诱导的人DSM条的收缩。此外，100 μM的CLQ能显著抑制电场刺激（EFS）引起的人DSM条的自发收缩和收缩。在轻微收缩后，CLQ （1 mM）完全放松了碳巴酚诱导的小鼠DSM条收缩。此外，地那铵和奎宁浓度依赖性地降低了碳巴酚诱导的小鼠DSM条收缩。最后，我们证明CLQ治疗可显著抑制部分膀胱出口梗阻（PBOO）小鼠的膀胱过动症（OAB）症状。总之，我们首次提供了尿DSM中TAS2Rs存在的证据，并证明TAS2Rs可能是OAB的潜在靶点。这些发现为今后开发治疗OAB的药物开辟了新的途径。
Bitter taste receptors (TAS2Rs) are traditionally thought to be expressed exclusively on the taste buds of the tongue. However, accumulating evidence has indicated that this receptor family performs non-gustatory functions outside the mouth in addition to taste. Here, we examined the role of TAS2Rs in human and mouse detrusor smooth muscle (DSM). We showed that mRNA for various TAS2R subtypes was expressed in both human and mouse detrusor smooth muscle (DSM) at distinct levels. Chloroquine (CLQ), an agonist for TAS2Rs, concentration-dependently relaxed carbachol- and KCl-induced contractions of human DSM strips. Moreover, 100 μM of CLQ significantly inhibited spontaneous and electrical field stimulation (EFS)-induced contractions of human DSM strips. After a slight contraction, CLQ (1 mM) entirely relaxed carbachol-induced contraction of mouse DSM strips. Furthermore, denatonium and quinine concentration-dependently decreased carbachol-induced contractions of mouse DSM strips. Finally, we demonstrated that CLQ treatment significantly suppressed the overactive bladder (OAB) symptoms of mice with partial bladder outlet obstruction (PBOO). In conclusion, we for the first time provide evidence of the existence of TAS2Rs in the urinary DSM and demonstrate that TAS2Rs may represent a potential target for OAB. These findings open a new approach to develop drugs for OAB in the future.
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