A Taste Receptor Required for the Caffeine Response In Vivo

Seok Jun Moon, Michael Köttgen, Yuchen Jiao, Hong Xu, Craig Montell

Research output: Contribution to journalArticlepeer-review

203 Citations (Scopus)


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, 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.

Original languageEnglish
Pages (from-to)1812-1817
Number of pages6
JournalCurrent Biology
Issue number18
Publication statusPublished - 2006 Sept 19

Bibliographical note

Funding Information:
We thank Drs. Hubert Amrein for the P[Gr66a-Gal4] flies, Jin Zhang for the HEK293 cells expressing the derivative of ICUE1, and Tao Wang for helpful comments on the manuscript. This work was supported by grants to M.K. from the Polycystic Kidney Disease Foundation and to C.M. from the NIDCD (DC007864).

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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