CHARACTERIZATION AND SOLUBILIZATION OF BITTER-RESPONSIVE RECEPTORS THAT COUPLE TO GUSTDUCIN

The tastes of many bitter and sweet compounds are thought to be transd uced via guanine nucleotide binding protein (G-protein)-coupled recept ors, although the biochemical nature of these receptors is poorly unde rstood at present. Gustducin, a taste-specific G-protein closely relat ed to the transducins, is a key component in transducing the responses to compounds that humans equate with bitter and sweet. Rod transducin , which is also expressed in taste receptor cells, can be activated by the bitter compound denatonium in the presence of bovine taste membra nes. In this paper, we show that gustducin is expressed in bovine tast e tissue and that both gustducin and transducin, in the presence of bo vine taste membranes, can be activated specifically by several bitter compounds, including denatonium, quinine, and strychnine. We also demo nstrate that the activation in response to denatonium of gustducin by presumptive bitter-responsive receptors present in taste membranes dep ends on an interaction with the C terminus of gustducin and requires G -protein py subunits to provide the receptor-interacting heterotrimer. The taste receptor-gustducin interaction can be competitively inhibit ed by peptides derived from the sites of interaction of rhodopsin and transducin. Finally, as the initial step toward purifying taste recept ors, we have solubilized this bitter-responsive taste receptor and mai ntained its biological activity.