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In teleosts, sequence homologues of the mammalian CaSR have been described but their function in sensing amino acids remains elusive, including in Atlantic salmon (<jats:italic>Salmo salar<\/jats:italic>), an important aquaculture species. This study investigated the activation of Atlantic salmon Casr (asCasr)-mediated signaling pathways\u2014G<jats:sub>q<\/jats:sub>, G<jats:sub>i<\/jats:sub>, and ERK1\/2\u2014by six selected L-amino acids (histidine, tryptophan, phenylalanine, isoleucine, leucine and valine) and by Ca<jats:sup>2+<\/jats:sup>. Using a Flp-In-HEK293 cell line stably expressing asCasr, we confirmed activation of all three pathways. L-histidine, L-phenylalanine, and L-tryptophan triggered G<jats:sub>i<\/jats:sub> signaling independent of Ca\u00b2\u207a. Notably, no Ca\u00b2\u207a concentrations induced G<jats:sub>i<\/jats:sub> activation, but IP<jats:sub>1<\/jats:sub> production increased in a concentration-dependent manner. L-histidine was the only amino acid to activate the G<jats:sub>q<\/jats:sub> pathway without Ca\u00b2\u207a, and this response was amplified by the presence of Ca\u00b2\u207a. In the presence of 2.5 mM Ca\u00b2\u207a, L-phenylalanine and L-tryptophan also activated G<jats:sub>q<\/jats:sub> signaling in a concentration-dependent manner. Additionally, in the presence of 10 mM Ca\u00b2\u207a, L-histidine, L-phenylalanine, and L-tryptophan triggered ERK phosphorylation. These findings establish asCasr as a functional homologue of mammalian CaSR, activated in a concentration-dependent manner by L-amino acids with an aromatic ring.<\/jats:p>","DOI":"10.1038\/s41598-025-97483-5","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T04:21:23Z","timestamp":1744863683000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Activation profile of the Atlantic salmon (Salmo salar) calcium-sensing receptor (Casr) by selected L-amino acids"],"prefix":"10.1038","volume":"15","author":[{"given":"Ana S.","family":"Gomes","sequence":"first","affiliation":[]},{"given":"Virginie","family":"G\u00e9l\u00e9bart","sequence":"additional","affiliation":[]},{"given":"Rute C.","family":"F\u00e9lix","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o C.R.","family":"Cardoso","sequence":"additional","affiliation":[]},{"given":"Fabian","family":"Zimmermann","sequence":"additional","affiliation":[]},{"given":"Floriana","family":"Lai","sequence":"additional","affiliation":[]},{"given":"Deborah M.","family":"Power","sequence":"additional","affiliation":[]},{"given":"Ivar","family":"R\u00f8nnestad","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"97483_CR1","doi-asserted-by":"publisher","unstructured":"D\u00edaz-Soto, G., Rocher, A., Garc\u00eda-Rodr\u00edguez, C., N\u00fa\u00f1ez, L. & Villalobos, C. 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