Modulation of sweet taste by umami compounds via sweet taste receptor subunit hT1R2.

Although the five basic taste qualities-sweet, sour, bitter, salty and umami-can be recognized by the respective gustatory system, interactions between these taste qualities are often experienced when food is consumed. Specifically, the umami taste has been investigated in terms of whether it enhances or reduces the other taste modalities. These studies, however, are based on individual perception and not on a molecular level. In this study we investigated umami-sweet taste interactions using umami compounds including monosodium glutamate (MSG), 5'-mononucleotides and glutamyl-dipeptides, glutamate-glutamate (Glu-Glu) and glutamate-aspartic acid (Glu-Asp), in human sweet taste receptor hT1R2/hT1R3-expressing cells. The sensitivity of sucrose to hT1R2/hT1R3 was significantly attenuated by MSG and umami active peptides but not by umami active nucleotides. Inhibition of sweet receptor activation by MSG and glutamyl peptides is obvious when sweet receptors are activated by sweeteners that target the extracellular domain (ECD) of T1R2, such as sucrose and acesulfame K, but not by cyclamate, which interact with the T1R3 transmembrane domain (TMD). Application of umami compounds with lactisole, inhibitory drugs that target T1R3, exerted a more severe inhibitory effect. The inhibition was also observed with F778A sweet receptor mutant, which have the defect in function of T1R3 TMD. These results suggest that umami peptides affect sweet taste receptors and this interaction prevents sweet receptor agonists from binding to the T1R2 ECD in an allosteric manner, not to the T1R3. This is the first report to define the interaction between umami and sweet taste receptors.

Leptin increases temperature-dependent chorda tympani nerve responses to sucrose in mice.

Leptin receptors are present in taste buds and previous research indicates that leptin administration modified electrophysiological and behavioral responses to sweet taste. It is now known that sweet taste is temperature dependent. We examined the influence of (1) stimulus temperature on chorda tympani (CT) nerve responses to sucrose, saccharin and NH(4)Cl; and (2) leptin administration on CT nerve responses to sucrose, saccharin and other basic taste stimuli at 35°C that maximized sweet-taste sensitivity in C57BL/6 mice. We found that the CT nerve responded with greater magnitude to sucrose and saccharin as stimulus temperature increased from 23 to 35°C and then declined at higher temperatures. In contrast, the CT nerve responses to NH(4)Cl increased in magnitude as temperature increased from 23 to 44°C. We also showed that leptin selectively increased the CT nerve responses to sucrose at 35°C in both fasted and free-fed mice. The responses of mice treated with the saline vehicle did not change. Our findings are consistent with the notion that leptin binds with its receptors in fungiform taste buds and alters the message conveyed by sugar-responsive neurons to the brain.