Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha-gustducin-dependent fall in cyclic nucleotides

Current evidence points to the existence of multiple processesfor bitter taste transduction. Previous work demonstrated involvement of the polyphosphoinositide system and an -gustducin(G_gust)-mediated stimulation of phosphodiesterase inbitter taste transduction. Additionally, a taste-enriched G protein-subunit, G₁₃, colocalizes with G_gustand mediates the denatonium-stimulated production of inositol1,4,5-trisphosphate (IP₃). Using quench-flow techniques, weshow here that the bitter stimuli, denatonium and strychnine, inducerapid (50-100 ms) and transient reductions in cAMP and cGMP andincreases in IP₃ in murine taste tissue. This decrease ofcyclic nucleotides is inhibited by G_gust antibodies,whereas the increase in IP₃ is not affected by antibodiesto G_gust. IP₃ production is inhibited byantibodies specific to phospholipase C-₂(PLC-₂), a PLC isoform known to be activated byG-subunits. Antibodies to PLC-₃ or toPLC-₄ were without effect. These data suggest atransduction mechanism for bitter taste involving the rapid andtransient metabolism of dual second messenger systems, both mediatedthrough a taste cell G protein, likely composed ofG_gust//₁₃, with both systems beingsimultaneously activated in the same bitter-sensitive taste receptor cell.