---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '19706'
abstract:
- lang: eng
  text: 'The importance of astrocytic l-lactate (LL) for normal functioning of neural
    circuits such as those regulating learning/memory, sleep/wake state, autonomic
    homeostasis, or emotional behaviour is being increasingly recognised. l-Lactate
    can act on neurones as a metabolic or redox substrate, but transmembrane receptor
    targets are also emerging. A comparative review of the hydroxy-carboxylic acid
    receptor (HCA1, formerly known as GPR81), Olfactory Receptor Family 51 Subfamily
    E Member 2 (OR51E2), and orphan receptor GPR4 highlights differences in their
    LL sensitivity, pharmacology, intracellular coupling, and localisation in the
    brain. In addition, a putative Gs-coupled receptor on noradrenergic neurones,
    LLRx, which we previously postulated, remains to be identified. Next-generation
    sequencing revealed several orphan receptors expressed in locus coeruleus neurones.
    Screening of a selection of these suggests additional LL-sensitive receptors:
    GPR180 which inhibits and GPR137 which activates intracellular cyclic AMP signalling
    in response to LL in a heterologous expression system. To further characterise
    binding of LL at LLRx, we carried out a structure–activity relationship study
    which demonstrates that carboxyl and 2-hydroxyl moieties of LL are essential for
    triggering d-lactate-sensitive noradrenaline release in locus coeruleus, and that
    the size of the LL binding pocket is limited towards the methyl group position.
    The evidence accumulating to date suggests that LL acts via multiple receptor
    targets to modulate distinct brain functions.'
acknowledgement: This work was supported by grants from BBSRC BB/L019396/1, and MRC
  MR/L020661/1. David Kleinfeld for his gift of CNiFER cells, Lesley Arberry for expert
  technical support, Andrew Herman for support with FACS sorting.
article_processing_charge: Yes
article_type: original
author:
- first_name: Valentina
  full_name: Mosienko, Valentina
  last_name: Mosienko
- first_name: Seyed
  full_name: Rasooli-Nejad, Seyed
  last_name: Rasooli-Nejad
- first_name: Kasumi
  full_name: Kishi, Kasumi
  id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
  last_name: Kishi
- first_name: Matt
  full_name: De Both, Matt
  last_name: De Both
- first_name: David
  full_name: Jane, David
  last_name: Jane
- first_name: Matt J.
  full_name: Huentelman, Matt J.
  last_name: Huentelman
- first_name: Sergey
  full_name: Kasparov, Sergey
  last_name: Kasparov
- first_name: Anja G.
  full_name: Teschemacher, Anja G.
  last_name: Teschemacher
citation:
  ama: Mosienko V, Rasooli-Nejad S, Kishi K, et al. Putative receptors underpinning
    L-Lactate signalling in locus coeruleus. <i>Neuroglia</i>. 2018;1(2):365-380.
    doi:<a href="https://doi.org/10.3390/neuroglia1020025">10.3390/neuroglia1020025</a>
  apa: Mosienko, V., Rasooli-Nejad, S., Kishi, K., De Both, M., Jane, D., Huentelman,
    M. J., … Teschemacher, A. G. (2018). Putative receptors underpinning L-Lactate
    signalling in locus coeruleus. <i>Neuroglia</i>. MDPI. <a href="https://doi.org/10.3390/neuroglia1020025">https://doi.org/10.3390/neuroglia1020025</a>
  chicago: Mosienko, Valentina, Seyed Rasooli-Nejad, Kasumi Kishi, Matt De Both, David
    Jane, Matt J. Huentelman, Sergey Kasparov, and Anja G. Teschemacher. “Putative
    Receptors Underpinning L-Lactate Signalling in Locus Coeruleus.” <i>Neuroglia</i>.
    MDPI, 2018. <a href="https://doi.org/10.3390/neuroglia1020025">https://doi.org/10.3390/neuroglia1020025</a>.
  ieee: V. Mosienko <i>et al.</i>, “Putative receptors underpinning L-Lactate signalling
    in locus coeruleus,” <i>Neuroglia</i>, vol. 1, no. 2. MDPI, pp. 365–380, 2018.
  ista: Mosienko V, Rasooli-Nejad S, Kishi K, De Both M, Jane D, Huentelman MJ, Kasparov
    S, Teschemacher AG. 2018. Putative receptors underpinning L-Lactate signalling
    in locus coeruleus. Neuroglia. 1(2), 365–380.
  mla: Mosienko, Valentina, et al. “Putative Receptors Underpinning L-Lactate Signalling
    in Locus Coeruleus.” <i>Neuroglia</i>, vol. 1, no. 2, MDPI, 2018, pp. 365–80,
    doi:<a href="https://doi.org/10.3390/neuroglia1020025">10.3390/neuroglia1020025</a>.
  short: V. Mosienko, S. Rasooli-Nejad, K. Kishi, M. De Both, D. Jane, M.J. Huentelman,
    S. Kasparov, A.G. Teschemacher, Neuroglia 1 (2018) 365–380.
date_created: 2025-05-18T22:02:51Z
date_published: 2018-12-01T00:00:00Z
date_updated: 2025-05-19T08:28:40Z
day: '01'
ddc:
- '570'
department:
- _id: AnKi
doi: 10.3390/neuroglia1020025
file:
- access_level: open_access
  checksum: cadb56618f72edf4703b6a9855e84baa
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  creator: dernst
  date_created: 2025-05-19T08:20:19Z
  date_updated: 2025-05-19T08:20:19Z
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file_date_updated: 2025-05-19T08:20:19Z
fulldoi: https://doi.org/10.3390/neuroglia1020025
has_accepted_license: '1'
intvolume: '         1'
issue: '2'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 365-380
publication: Neuroglia
publication_identifier:
  eissn:
  - 2571-6980
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: Putative receptors underpinning L-Lactate signalling in locus coeruleus
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2018'
...