title: Involvement of the calcium-sensing receptor in human taste perception.
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.
authors.affiliation: Pharmaceutical Research Laboratories, Ajinomoto Company, Incorporated, Kawasaki 210-8681, Japan.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Ohsu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Amino
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagasaki
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yamanaka
authors.forename: Sen
authors.initials: S
authors.lastname: Takeshita
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hatanaka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Naohiro
authors.initials: N
authors.lastname: Miyamura
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Eto
mesh_terms: 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
chemical_list: 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