title: Denatonium and 6-n-Propyl-2-thiouracil, Agonists of Bitter Taste Receptor, Inhibit Contraction of Various Types of Smooth Muscles in the Rat and Mouse.
abstract: Recently the global expression of taste 2 receptors (TAS2Rs) on smooth muscle cells in human airways was demonstrated. Here, the effects of agonists of taste receptor, type 2, denatonium and 6-n-propyl-2-thiouracil, on smooth-muscle contraction were examined in the rat and mouse. Contractions induced by carbachol (CCh), high K(+), and sodium fluoride, but not calyculin-A, were inhibited significantly in the presence of a TAS2R agonist in the bronchial smooth muscle of mice. The contraction induced by CCh was inhibited by TAS2R agonists in ileal smooth muscle. Phenylephrine-induced contraction was also inhibited by TAS2R agonists in aortic smooth muscle. Gastrointestinal motility and blood pressure were attenuated by administration of TAS2R agonists in vivo. These findings suggest that TAS2R may be receptor for endogenous biologically active substances as well as for bitter tastes on the tongue. TAS2R signaling could be employed in the development of anti-asthmatic, anti-spasmodic, and anti-hypertensive drugs.
authors.affiliation: Department of Analytical Pathophysiology, Division of Pharmacy Professional Development and Research, Hoshi University.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kai
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Chiba
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D011441:Propylthiouracil / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D012969:Sodium Fluoride / Q000494:pharmacology
chemical_list: D002217:Carbachol; D011188:Potassium; D011441:Propylthiouracil; D000644:Quaternary Ammonium Compounds; D043562:Receptors, G-Protein-Coupled; D012969:Sodium Fluoride; C043414:denatonium