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Amino acid sensing in hypothalamic tanycytes via umami taste receptors
OBJECTIVE: Hypothalamic tanycytes are glial cells that line the wall of the third ventricle and contact the cerebrospinal fluid (CSF). While they are known to detect glucose in the CSF we now show that tanycytes also detect amino acids, important nutrients that signal satiety. METHODS: Ca(2+) imagin...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681271/ https://www.ncbi.nlm.nih.gov/pubmed/29107294 http://dx.doi.org/10.1016/j.molmet.2017.08.015 |
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author | Lazutkaite, Greta Soldà, Alice Lossow, Kristina Meyerhof, Wolfgang Dale, Nicholas |
author_facet | Lazutkaite, Greta Soldà, Alice Lossow, Kristina Meyerhof, Wolfgang Dale, Nicholas |
author_sort | Lazutkaite, Greta |
collection | PubMed |
description | OBJECTIVE: Hypothalamic tanycytes are glial cells that line the wall of the third ventricle and contact the cerebrospinal fluid (CSF). While they are known to detect glucose in the CSF we now show that tanycytes also detect amino acids, important nutrients that signal satiety. METHODS: Ca(2+) imaging and ATP biosensing were used to detect tanycyte responses to l-amino acids. The downstream pathway of the responses was determined using ATP receptor antagonists and channel blockers. The receptors were characterized using mice lacking the Tas1r1 gene, as well as an mGluR4 receptor antagonist. RESULTS: Amino acids such as Arg, Lys, and Ala evoke Ca(2+) signals in tanycytes and evoke the release of ATP via pannexin 1 and CalHM1, which amplifies the signal via a P2 receptor dependent mechanism. Tanycytes from mice lacking the Tas1r1 gene had diminished responses to lysine and arginine but not alanine. Antagonists of mGluR4 greatly reduced the responses to alanine and lysine. CONCLUSION: Two receptors previously implicated in taste cells, the Tas1r1/Tas1r3 heterodimer and mGluR4, contribute to the detection of a range of amino acids by tanycytes in CSF. |
format | Online Article Text |
id | pubmed-5681271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-56812712017-11-20 Amino acid sensing in hypothalamic tanycytes via umami taste receptors Lazutkaite, Greta Soldà, Alice Lossow, Kristina Meyerhof, Wolfgang Dale, Nicholas Mol Metab Original Article OBJECTIVE: Hypothalamic tanycytes are glial cells that line the wall of the third ventricle and contact the cerebrospinal fluid (CSF). While they are known to detect glucose in the CSF we now show that tanycytes also detect amino acids, important nutrients that signal satiety. METHODS: Ca(2+) imaging and ATP biosensing were used to detect tanycyte responses to l-amino acids. The downstream pathway of the responses was determined using ATP receptor antagonists and channel blockers. The receptors were characterized using mice lacking the Tas1r1 gene, as well as an mGluR4 receptor antagonist. RESULTS: Amino acids such as Arg, Lys, and Ala evoke Ca(2+) signals in tanycytes and evoke the release of ATP via pannexin 1 and CalHM1, which amplifies the signal via a P2 receptor dependent mechanism. Tanycytes from mice lacking the Tas1r1 gene had diminished responses to lysine and arginine but not alanine. Antagonists of mGluR4 greatly reduced the responses to alanine and lysine. CONCLUSION: Two receptors previously implicated in taste cells, the Tas1r1/Tas1r3 heterodimer and mGluR4, contribute to the detection of a range of amino acids by tanycytes in CSF. Elsevier 2017-09-14 /pmc/articles/PMC5681271/ /pubmed/29107294 http://dx.doi.org/10.1016/j.molmet.2017.08.015 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Article Lazutkaite, Greta Soldà, Alice Lossow, Kristina Meyerhof, Wolfgang Dale, Nicholas Amino acid sensing in hypothalamic tanycytes via umami taste receptors |
title | Amino acid sensing in hypothalamic tanycytes via umami taste receptors |
title_full | Amino acid sensing in hypothalamic tanycytes via umami taste receptors |
title_fullStr | Amino acid sensing in hypothalamic tanycytes via umami taste receptors |
title_full_unstemmed | Amino acid sensing in hypothalamic tanycytes via umami taste receptors |
title_short | Amino acid sensing in hypothalamic tanycytes via umami taste receptors |
title_sort | amino acid sensing in hypothalamic tanycytes via umami taste receptors |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681271/ https://www.ncbi.nlm.nih.gov/pubmed/29107294 http://dx.doi.org/10.1016/j.molmet.2017.08.015 |
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