Bitter taste transduced by PLC-beta(2)-dependent rise in IP3 and alpha-gustducin-dependent fall in cyclic nucleotides

Current evidence points to the existence of multiple processes for bitter t aste transduction. Previous work demonstrated involvement of the polyphosph oinositide system and an alpha -gustducin (G alpha (gust))-mediated stimula tion of phosphodiesterase in bitter taste transduction. Additionally, a tas te-enriched G protein gamma -subunit, G gamma (13), colocalizes with G alph a (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 tra nsient reductions in cAMP and cGMP and increases in IP3 in murine taste tis sue. This decrease of cyclic nucleotides is inhibited by G alpha (gust) ant ibodies, whereas the increase in IP3 is not affected by antibodies to G alp ha (gust). IP3 production is inhibited by antibodies specific to phospholip ase C-beta (2) (PLC-beta (2)), a PLC isoform known to be activated by G bet a gamma -subunits. Antibodies to PLC-beta (3) or to PLC-beta (4) were witho ut effect. These data suggest a transduction mechanism for bitter taste inv olving 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.