title: Activation of bitter taste receptors (tas2rs) relaxes detrusor smooth muscle and suppresses overactive bladder symptoms.
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.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhai
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Urology, Beijing Jishuitan Hospital, Beijing, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Eric
authors.initials: E
authors.lastname: Nyirimigabo
authors.affiliation: Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Mi
authors.affiliation: Department of Gastroenterology, Peking University First Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute for Medical Biology, College of Life Sciences, South-Central University for Nationalities, Wuhan, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Urology, Beijing Jishuitan Hospital, Beijing, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Man
authors.affiliation: Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Guangju
authors.initials: G
authors.lastname: Ji
mesh_terms: D000368:Aged; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D053201:Urinary Bladder, Overactive / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000098706:Taste Receptors, Type 2
chemical_list: D018501:Antirheumatic Agents; D002316:Cardiotonic Agents; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D002738:Chloroquine; D002217:Carbachol
keywords: Gerotarget; bitter taste receptors; chloroquine; detrusor smooth muscle; human; mouse; overactive bladder