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However, kokumi has not been well studied in gustatory physiology, and the underlying neuroscientific mechanisms remain largely unexplored. Our previous research demonstrated that ornithine (L-ornithine), which is abundant in shijimi clams, enhanced taste preferences in mice. The present study aimed to build on these findings and investigate the mechanisms responsible for kokumi in rats. In two-bottle preference tests, the addition of ornithine, at a low concentration that did not increase the favorability of this substance alone, enhanced the animals\u2019 preferences for umami, sweet, fatty, salty, and bitter solutions, with the intake of monosodium glutamate showing the most significant increase. Additionally, a mixture of umami and ornithine synergistically induced significant responses in the chorda tympani nerve, which transmits taste information to the brain from the anterior part of the tongue. The observed preference enhancement and increase in taste-nerve response were abolished by antagonists of the G-protein-coupled receptor family C group 6 subtype A (GPRC6A). Furthermore, immunohistochemical analysis indicated that GPRC6A was expressed in a subset of type II taste cells in rat fungiform papillae. These results provide new insights into flavor-enhancement mechanisms, confirming that ornithine is a kokumi substance and GPRC6A is a novel kokumi receptor.<\/jats:p>","DOI":"10.7554\/elife.101629","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T12:25:47Z","timestamp":1732537547000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.101629","source":"Crossref","is-referenced-by-count":5,"title":["GPRC6A as a novel kokumi receptor responsible for enhanced taste preferences by ornithine"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0132-2936","authenticated-orcid":true,"given":"Takashi","family":"Yamamoto","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03b657f73","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Nutrition, Faculty of Human Sciences, Kio University","place":["Nara, 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