In addition to the well-accepted taste receptors corresponding to the 6 basic taste qualities, sweet, salty, sour, bitter, umami, and fatty, another type of taste receptor, calcium-sensing receptor (CaSR), is located in taste bud cells. CaSR is called the kokumi receptor because its agonists induce koku (or kokumi), a Japanese word meaning the enhancement of flavor characteristics, such as thickness, mouthfulness, and continuity. Kokumi is an important factor in enhancing food palatability. γ-Glu-Val-Gly (EVG) is the most potent agonist of CaSR, which induces a strong kokumi flavor. However, no behavioral studies have been documented in animals using EVG. Here, we show that EVG at low concentrations that do not elicit a taste of its own enhances preferences for umami, fat, and sweet taste solutions in rats. An increased preference for inosine monophosphate (IMP) and Intralipos was the most dominant effect. NPS-2143, an antagonist of CaSR, abolished the additive effect of EVG on IMP and Intralipos solutions. These effects of EVG on taste stimuli are thought to occur in the oral cavity, because the effects of EVG were confirmed in a brief exposure test. The additive effects on IMP and Intralipos remained after the transection of the chorda tympani, indicating that these effects also occur in the palate and/or posterior part of the tongue. Moreover, the additive effects of EVG were verified in electrophysiological taste nerve responses. These results may partially provide the underlying mechanisms for EVG to induce kokumi flavor in humans.

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