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Amino acid sensing in hypothalamic tanycytes via umami taste receptors
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Lazutkaite, Greta, Soldà, Alice, Lossow, Kristina, Meyerhof, Wolfgang and Dale, Nicholas (2017) Amino acid sensing in hypothalamic tanycytes via umami taste receptors. Molecular Metabolism, 6 (11). pp. 1480-1492. doi:10.1016/j.molmet.2017.08.015 ISSN 2212-8778.
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WRAP-amino-acid-hypothalamic-tanycytes-Dale-2017.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (6Mb) |
Official URL: http://dx.doi.org/10.1016/j.molmet.2017.08.015
Abstract
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:
Ca2+ 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 Ca2+ 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.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QP Physiology | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Amino acids in human nutrition, Hypothalamus, Homeostasis, Neuroglia, Cerebrospinal fluid, Neurotrophic functions | ||||||||
Journal or Publication Title: | Molecular Metabolism | ||||||||
Publisher: | Elsevier BV | ||||||||
ISSN: | 2212-8778 | ||||||||
Official Date: | November 2017 | ||||||||
Dates: |
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Volume: | 6 | ||||||||
Number: | 11 | ||||||||
Page Range: | pp. 1480-1492 | ||||||||
DOI: | 10.1016/j.molmet.2017.08.015 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 19 September 2017 | ||||||||
Date of first compliant Open Access: | 19 September 2017 | ||||||||
Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), University of Warwick Chancellor's Scholarship | ||||||||
Grant number: | BB/M022692/1 |
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