Blocking taste receptor activation of gustducin inhibits gustatory responses to bitter compounds

Gustducin, a transducin-like guanine nucleotide-binding regulatory protein (G protein), and transducin are expressed in taste receptor cells where the y are thought to mediate taste transduction, Gustducin and transducin are a ctivated in the presence of bovine taste membranes by several compounds tha t humans perceive to be bitter. We have monitored this activation with an i n vitro assay to identify compounds that inhibited taste receptor activatio n of transducin by bitter tastants: AMP and chemically related compounds in hibited in vitro responses to several bitter compounds (e,g,, denatonium, q uinine, strychnine, and atropine). AMP also inhibited behavioral and electr ophysiological responses of mice to bitter tastants, but not to NaCl, HCl, or sucrose. GMP, although chemically similar to AMP, inhibited neither the bitter-responsive taste receptor activation of transducin nor the gustatory responses of mice to bitter compounds. AMP and certain related compounds m ay bind to bitter-responsive taste receptors or interfere with receptor-G p rotein coupling to serve as naturally occurring taste modifiers.