RECEPTORS THAT MEDIATE SWEETNESS - INFERENCES FROM BIOCHEMICAL, ELECTROPHYSIOLOGICAL AND PSYCHOPHYSICAL DATA

Identification, isolation, and characterization of taste receptors for sweet compounds have not yet been accomplished due to inadequate bioc hemical techniques appropriate for studying receptor binding in gustat ion. However, a series of biochemical, electrophysiological, and psych ophysical studies suggest that proteinaceous receptors coupled to the G-protein/adenylate cyclase second messenger cascade mediate sweet tas te for some compounds. Other second messenger systems (e.g. the phosph atidyl inositol system) as well as ion channels and non-receptor mecha nisms may also be involved. There is ample evidence that multiple type s of sweet receptors are required to transduce signals for the many ch emical classes of compounds that taste sweet: e.g. low molecular weigh t carbohydrates, aminoacyl. sugars, amino acids, peptides, proteins, t erpenoids, chlorinated hydrocarbons, halogenated sugars, N-sulfonyl am ides, sulfamates, polyketides, anilines, and ureas. Evidence for multi ple receptors comes from a variety of studies including: 1) use of swe etness inhibitors (e.g. gymnemic acid or phenoxyalkanoic acid compound s), 2) electrophysiological recordings using modifiers of second messe nger systems, 3) cross-adaptation studies, 4) sweetener mixtures that produce synergy, and 5) structure-activity studies combined with molec ular modeling. When adequate biochemical techniques are finally achiev ed for isolating and characterizing sweet receptor proteins, the ratio nal and systematic design of sweeteners by computer will replace seren dipity in the discovery of new sweetener compounds.