Receptors that mediate sweetness: Inferences from biochemical, electrophysiological and psychophysical data

Abstract

Identification, isolation, and characterization of taste receptors for sweet compounds have not yet been accomplished due to inadequate biochemical techniques appropriate for studying receptor binding in gustation. However, a series of biochemical, electrophysiological, and psychophysical studies suggest that proteinaceous receptors coupled to the G-protein/adenylate cyclase second messenger cascade mediate sweet taste for some compounds. Other second messenger systems (e.g. the phosphatidyl inositol system) as well as ion channels and non-receptor mechanisms may also be involved. There is ample evidence that multiple types of sweet receptors are required to transduce signals for the many chemical classes of compounds that taste sweet: e.g. low molecular weight carbohydrates, aminoacyl sugars, amino acids, peptides, proteins, terpenoids, chlorinated hydrocarbons, halogenated sugars, N-sulfonyl amides, sulfamates, polyketides, anilines, and ureas. Evidence for multiple receptors comes from a variety of studies including: 1) use of sweetness inhibitors (e.g. gymnemic acid or phenoxyalkanoic acid compounds), 2) electrophysiological recordings using modifiers of second messenger systems, 3) cross-adaptation studies, 4) sweetener mixtures that produce synergy, and 5) structure-activity studies combined with molecular modeling. When adequate biochemical techniques are finally achieved for isolating and characterizing sweet receptor proteins, the rational and systematic design of sweeteners by computer will replace serendipity in the discovery of new sweetener compounds.