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A Taste Receptor Required for the Caffeine Response In Vivo

 Seok Jun Moon  ;  Michael Köttgen  ;  Yuchen Jiao  ;  Hong Xu  ;  Craig Montell 
 CURRENT BIOLOGY, Vol.16(18) : 1812-1817, 2006 
Journal Title
Issue Date
Animals ; Caffeine/chemistry ; Caffeine/metabolism ; Caffeine/pharmacology* ; Chemoreceptor Cells/metabolism ; Chemoreceptor Cells/physiology* ; Drosophila/drug effects ; Drosophila/metabolism* ; Drosophila/physiology ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila Proteins/physiology* ; Gene Deletion ; Neurons, Afferent/drug effects ; Neurons, Afferent/metabolism* ; Phosphodiesterase Inhibitors/metabolism ; Phosphodiesterase Inhibitors/pharmacology ; Receptors, G-Protein-Coupled/metabolism ; Receptors, G-Protein-Coupled/physiology* ; Theobromine/metabolism ; Theobromine/pharmacology
Caffeine is a methylxanthine present in the coffee tree, tea plant, and other naturally occurring sources and is among the most commonly consumed drugs worldwide. Whereas the pharmacological action of caffeine has been studied extensively, relatively little is known concerning the molecular mechanism through which this substance is detected as a bitter compound. Unlike most tastants, which are detected through cell-surface G protein-coupled receptors, it has been proposed that caffeine and related methylxanthines activate taste-receptor cells through inhibition of a cyclic nucleotide phosphodiesterase (PDE) [1]. Here, we show that the gustatory receptor Gr66a is expressed in the dendrites of Drosophila gustatory receptor neurons and is essential for the caffeine response. In a behavioral assay, the aversion to caffeine was specifically disrupted in flies missing Gr66a. Caffeine-induced action potentials were also eliminated, as was the response to theophylline, the methylxanthine in tea. The Gr66a mutant exhibited normal tastant-induced action potentials upon presentation of theobromine, a methylxanthine in cocoa. Given that theobromine and caffeine inhibit PDEs with equal potencies 2 and 3, these data further support the role of Gr66a rather than a PDE in mediating the caffeine response. Gr66a is the first gustatory receptor shown to be essential for caffeine-induced behavior and activity of gustatory receptor cells in vivo.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Moon, Seok Jun(문석준) ORCID logo https://orcid.org/0000-0001-7282-2888
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