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 processes for bitter taste transduction. Previous work demonstrated involvement of the polyphosphoinositide system and an alpha-gustducin (Galpha(gust))-mediated stimulation of phosphodiesterase in bitter taste transduction. Additionally, a taste-enriched G protein gamma-subunit, Ggamma(13), colocalizes with Galpha(gust) and mediates the denatonium-stimulated production of inositol 1,4,5-trisphosphate (IP(3)). 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 IP(3) in murine taste tissue. This decrease of cyclic nucleotides is inhibited by Galpha(gust) antibodies, whereas the increase in IP(3) is not affected by antibodies to Galpha(gust). IP(3) production is inhibited by antibodies specific to phospholipase C-beta(2) (PLC-beta(2)), a PLC isoform known to be activated by Gbetagamma-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 Galpha(gust)/beta/gamma(13), with both systems being simultaneously activated in the same bitter-sensitive taste receptor cell.
Department of Basic Science and Craniofacial Biology, Division of Biological Science, Medicine, and Surgery, New York University College of Dentistry, 345 E. 24th St., New York, NY 10010, USA.
W
W
Yan
G
G
Sunavala
S
S
Rosenzweig
M
M
Dasso
J G
JG
Brand
A I
AI
Spielman
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D018684:Glycine Agents / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D054799:Phospholipase C beta; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D013649:Taste / Q000502:physiology*; D013650:Taste Buds / Q000201:enzymology; D015293:Transducin / Q000276:immunology / Q000378:metabolism*; D010738:Type C Phospholipases / Q000276:immunology / Q000378:metabolism*
D000242:Cyclic AMP; D006152:Cyclic GMP; D018684:Glycine Agents; D015544:Inositol 1,4,5-Trisphosphate; D007527:Isoenzymes; D054799:Phospholipase C beta; D000644:Quaternary Ammonium Compounds; D013331:Strychnine; D015293:Transducin; D010738:Type C Phospholipases; C075192:gustducin; C043414:denatonium