Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Activation of bitter taste receptors (tas2rs) relaxes detrusor smooth muscle and suppresses overactive bladder symptoms

Kui Zhai, Zhiguang Yang, Xiaofei Zhu, Eric Nyirimigabo, Yue Mi, Yan Wang, Qinghua Liu, Libo Man, Shiliang Wu, Jie Jin and Guangju Ji _

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Oncotarget. 2016; 7:21156-21167. https://doi.org/10.18632/oncotarget.8549

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Abstract

Kui Zhai1,*, Zhiguang Yang1,*, Xiaofei Zhu2,*, Eric Nyirimigabo1, Yue Mi3, Yan Wang4, Qinghua Liu5, Libo Man2, Shiliang Wu3, Jie Jin3 and Guangju Ji1

1 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

2 Department of Urology, Beijing Jishuitan Hospital, Beijing, China

3 Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China

4 Department of Gastroenterology, Peking University First Hospital, Beijing, China

5 Institute for Medical Biology, College of Life Sciences, South-Central University for Nationalities, Wuhan, China

* Those authors have contributed equally to this work

Correspondence to:

Guangju Ji, email:

Jie Jin, email:

Keywords: bitter taste receptors, chloroquine, detrusor smooth muscle, human, mouse, overactive bladder, Gerotarget

Received: March 10, 2016 Accepted: March 20, 2016 Published: April 02, 2016

Abstract

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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