Elsevier

Molecular Metabolism

Volume 6, Issue 11, November 2017, Pages 1480-1492
Molecular Metabolism

Original Article
Amino acid sensing in hypothalamic tanycytes via umami taste receptors

https://doi.org/10.1016/j.molmet.2017.08.015Get rights and content
Under a Creative Commons license
open access

Highlights

  • Hypothalamic tanycytes can detect amino acids in cerebrospinal fluid.

  • The mechanism is taste receptor-dependent.

  • Tas1r1/Tas1r3 mediates responses to l-arginine and l-lysine.

  • mGluR4 mediates responses to l-alanine and partially those of l-lysine.

  • ATP release from tanycytes evoked by amino acids reaches into the arcuate nucleus.

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.

Keywords

Hypothalamic tanycytes
Taste receptors
Tas1r1/Tas1r3
mGluR4
Amino acids
Appetite

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Present address: Dept. of Chemistry “G. Ciamician”, University of Bologna, Via Selmi 2, 40126, Bologna, Italy.