Receptors for bitter, sweet and umami taste couple to inhibitory G protein signaling pathways.
Taste receptors are thought to couple to the G protein Galpha-gustducin to initiate signal transduction cascades leading to taste perception. To further characterize the G protein-coupling selectivity of these receptors, we expressed them in HEK293 cells and monitored the modulation of different signaling pathways upon stimulation. We found that the bitter compound cycloheximide induces phosphorylation of extracellular signal-regulated kinases1 and 2 (ERK 1/2) and inhibits cAMP accumulation in HEK293 cells expressing the mouse bitter T2R(5) receptor. These effects are totally abolished upon treatment with pertussis toxin. On the other hand, sweeteners and monosodium glutamate induce phosphorylation of ERK1/2 and inhibit cAMP accumulation in HEK293 cells expressing the human sweet T1R(2)/T1R(3) receptor and the human umami T1R(1)/T1R(3) receptor, respectively. The effects of these taste modalities are also prevented by treatment with pertussis toxin. Collectively, our results show that taste receptors can functionally couple to Galpha(i/o) proteins to transmit intracellular signals.
Ozeck
Mark
M
Senomyx, Inc., 11099 North Torrey Pines Road, La Jolla, CA 92037, USA.
Brust
Paul
P
Xu
Hong
H
Servant
Guy
G
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001218:Aspartame / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003494:Cyclamates / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D003513:Cycloheximide / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012439:Saccharin / Q000378:metabolism / Q000494:pharmacology; D012970:Sodium Glutamate / Q000378:metabolism / Q000494:pharmacology; D013395:Sucrose / Q000378:metabolism / Q000494:pharmacology; D013649:Taste / Q000187:drug effects* / Q000235:genetics; D013650:Taste Buds / Q000187:drug effects / Q000502:physiology*; D015293:Transducin / Q000502:physiology; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology; D000098706:Taste Receptors, Type 2
D000067956:Adenylyl Cyclase Inhibitors; D003494:Cyclamates; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; C075192:gustducin; D005576:Colforsin; D005632:Fructose; D013395:Sucrose; D014364:Tryptophan; D003513:Cycloheximide; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D015293:Transducin; D000262:Adenylyl Cyclases; D012439:Saccharin; D012970:Sodium Glutamate; D001218:Aspartame