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 alpha -gustducin (G alpha (gust))-mediated stimulation of phosphodiesterase in bitter taste transduction. Additionally, a taste-enriched G protein gamma -subunit, G gamma (13), colocalizes with G alpha (gust) and mediates the denatonium-stimulated production of inositol 1,4,5-trisphosphate (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 G alpha (gust) antibodies, whereas the increase in IP3 is not affected by antibodies to G alpha (gust). IP3 production is inhibited by antibodies specific to phospholipase C-beta (2) (PLC-beta (2)), a PLC isoform known to be activated by G beta gamma -subunits. Antibodies to PLC-beta (3) or to PLC-beta (4) 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 G alpha (gust)/beta/gamma (13), with both systems being simultaneously activated in the same bitter-sensitive taste receptor cell.