Abstract
By human sensory analyses, we found that various extracellular calcium-sensing receptor (CaSR) agonists enhance sweet, salty, and umami tastes, although they have no taste themselves. These characteristics are known as "kokumi taste" and often appear in traditional Japanese cuisine. Although GSH is a typical kokumi taste substance (taste enhancer), its mode of action is poorly understood. Here, we demonstrate how the kokumi taste is enhanced by the CaSR, a close relative of the class C G-protein-coupled receptors T1R1, T1R2, and T1R3 (sweet and umami receptors). We identified a large number of CaSR agonist gamma-glutamyl peptides, including GSH (gamma-Glu-Cys-Gly) and gamma-Glu-Val-Gly, and showed that these peptides elicit the kokumi taste. Further analyses revealed that some known CaSR agonists such as Ca(2+), protamine, polylysine, L-histidine, and cinacalcet (a calcium-mimetic drug) also elicit the kokumi taste and that the CaSR-specific antagonist, NPS-2143, significantly suppresses the kokumi taste. This is the first report indicating a distinct function of the CaSR in human taste perception.
Highlights
The extracellular calcium-sensing receptor (CaSR)2 [1] is a class C G-protein-coupled receptor consisting of 1078 amino acids
We demonstrate that the CaSR is involved in kokumi taste perception in humans and report the discovery of various CaSR agonist peptides, including ␥-glutamylvalylglycine (␥-Glu-Val-Gly), a potent kokumi taste substance
Amino acids have been reported to bind to the large extracellular Venus flytrap domain of the CaSR, a structure common to all members of class C G-proteincoupled receptors
Summary
CaSR, calcium-sensing receptor; hCaSR, human CaSR; MSG, monosodium glutamate; Abu, ␣-aminobutyric acid; PSE, point of subjective equivalence; RT, reverse transcription. It is presumed that the CaSR [8] or a specific calcium channel is involved, no research provides direct evidence for the involvement of the CaSR in human taste perception. Humans can identify five basic tastes, sweet, salty, sour, bitter, and umami, which are believed to be recognized by specific receptors and transduction pathways. The kokumi taste was first characterized by Ueda et al [9, 10], who isolated a kokumi taste substance from water extracts of garlic and onion and identified GSH as the main active ingredient. We demonstrate that the CaSR is involved in kokumi taste perception in humans and report the discovery of various CaSR agonist peptides, including ␥-glutamylvalylglycine (␥-Glu-Val-Gly), a potent kokumi taste substance
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