Bitter taste transduced by PLC-β₂-dependent rise in IP₃ and α-gustducin-dependent fall in cyclic nucleotides

Current evidence points to the existence of multiple processes for bitter taste transduction. Previous work demonstrated involvement of the polyphosphoinositide system and an α-gustducin (Gα_gust)-mediated stimulation of phosphodiesterase in bitter taste transduction. Additionally, a taste-enriched G protein γ-subunit, Gγ₁₃, colocalizes with Gα_gust and mediates the denatonium-stimulated production of inositol 1,4,5-triphosphate (IP₃). Using quench-flow techniques, we show here that the bitter stimuli, denatonium and strychnine, induce rapid (50-100 ms) and transient reductions in cAMP and cGMP and increases in IP₃ in murine taste tissue. This decrease of cyclic nucleotides is inhibited by Gα_gust antibodies, whereas the increase in IP₃ is not affected by antibodies to Gα_gust. IP₃ production is inhibited by antibodies specific to phospholipase C-β₂ (PLC-β₂), a PLC isoform known to be activated by Gβγ-subunits. Antibodies to PLC-β₃ or to PLC-β₄ were without effect. These data suggest a transduction mechanism for bitter taste involving the rapid and transient metabolism of dual second messenger systems, both mediated through a taste cell G protein, likely composed of Gα_gust/β/γ₁₃, with both systems being simultaneously activated in the same bitter-sensitive taste receptor cell.