h-89 and denatonium-saccharide

The taste-selective G protein, alpha-gustducin (alpha-gus) is homologous to alpha-transducin and activates phosphodiesterase (PDE) in vitro. alpha-Gus-knockout mice are compromized to bitter, sweet and umami taste stimuli, suggesting a central role in taste transduction. Here, we suggest a different role for Galpha-gus. In taste buds of alpha-gus-knockout mice, basal (unstimulated) cAMP levels are high compared to those of wild-type mice. Further, H-89, a cAMP-dependent protein kinase inhibitor, dramatically unmasks responses to the bitter tastant denatonium in gus-lineage cells of knockout mice. We propose that an important role of alpha-gus is to maintain cAMP levels tonically low to ensure adequate Ca2+ signaling.

Topics: Animals; Calcium Signaling; Cyclic AMP; Heterotrimeric GTP-Binding Proteins; Isoquinolines; Mice; Mice, Knockout; Protein Kinase Inhibitors; Quaternary Ammonium Compounds; Sulfonamides; Taste; Taste Buds