title: Stimulation of the extracellular Ca²⁺-sensing receptor by denatonium.
abstract: The extracellular Ca(2+)-sensing receptor (CASR) is a promiscuous G-protein-coupled receptor closely related to the taste receptors T1R1-T1R3. Here we analyzed the possibility that apart from being stimulated by external Ca(2+) and amino acids, the substances effective as tastants, CASR might serve as a receptor for other sapid compounds. CASR was heterologously expressed in HEK-293 cells, and their responsivity to a variety of bitter and sweet substances was examined. Among them, solely denatonium was found to stimulate Ca(2+) signaling in CASR-positive HEK-293 cells. Apparently, these Ca(2+) responses were specific, as those were inhibited by the CASR antagonist NSP-4123. Altogether, our findings indicate that denatonium stimulates CASR by shifting a dose-response curve for the principal CASR agonist Ca(2+) to lower concentrations.
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Institutional Street 3, Pushchino, Moscow Region 142290, Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Rogachevskaja
authors.forename: Gleb D
authors.initials: GD
authors.lastname: Churbanov
authors.forename: Marina F
authors.initials: MF
authors.lastname: Bystrova
authors.forename: Roman A
authors.initials: RA
authors.lastname: Romanov
authors.forename: Stanislav S
authors.initials: SS
authors.lastname: Kolesnikov
mesh_terms: D001218:Aspartame / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D044169:Receptors, Calcium-Sensing / Q000819:agonists* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000235:genetics; D013395:Sucrose / Q000031:analogs & derivatives / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D004151:Dipeptides; D006146:Guanidines; D000644:Quaternary Ammonium Compounds; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled; C099860:SC 45647; D013549:Sweetening Agents; C431926:taste receptors, type 1; C026879:sucrose octaacetate; D013395:Sucrose; D003513:Cycloheximide; C404525:neotame; D001218:Aspartame