Involvement of the calcium-sensing receptor in human taste perception.
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.
Ohsu
Takeaki
T
Pharmaceutical Research Laboratories, Ajinomoto Company, Incorporated, Kawasaki 210-8681, Japan.
Amino
Yusuke
Y
Nagasaki
Hiroaki
H
Yamanaka
Tomohiko
T
Takeshita
Sen
S
Hatanaka
Toshihiro
T
Maruyama
Yutaka
Y
Miyamura
Naohiro
N
Eto
Yuzuru
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D000069449:Cinacalcet; D005260:Female; D006494:Heparin Antagonists / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology; D006801:Humans; D007564:Japan; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013649:Taste / Q000187:drug effects / Q000502:physiology*; D055697:Taste Perception / Q000187:drug effects / Q000502:physiology; D014982:Xenopus laevis
D006494:Heparin Antagonists; C436740:N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine; D009281:Naphthalenes; D009842:Oligopeptides; D011479:Protamines; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D006639:Histidine; D002118:Calcium; D000069449:Cinacalcet