Stimulation of the extracellular Ca²⁺-sensing receptor by denatonium.
Olga A Rogachevskaja, Gleb D Churbanov, Marina F Bystrova, Roman A Romanov, Stanislav S Kolesnikov
Index: Biochem. Biophys. Res. Commun. 416(3-4) , 433-6, (2011)
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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.Copyright © 2011 Elsevier Inc. All rights reserved.
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