A taste receptor required for the caffeine response in vivo.
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) . 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 , 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.
Moon
Seok Jun
SJ
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Köttgen
Michael
M
Jiao
Yuchen
Y
Xu
Hong
H
Montell
Craig
C
D000818:Animals; D002110:Caffeine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002628:Chemoreceptor Cells / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology*; D013805:Theobromine / Q000378:metabolism / Q000494:pharmacology
D029721:Drosophila Proteins; D010726:Phosphodiesterase Inhibitors; D043562:Receptors, G-Protein-Coupled; D002110:Caffeine; D013805:Theobromine