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Cited by 47melanin and skin pigmentationNeuroscience and Neuropharmacology ResearchMelanoma and MAPK Pathways

Glutamate receptors on human melanocytes regulate the expression of MiTF

Hoogduijn, M. J., Hitchcock, I. S., Smit, N. P. M., Gillbro, J. M., Schallreuter, K. U., Genever, P. G.·2006·Pigment Cell Research
DOI 10.1111/j.1600-0749.2005.00284.x
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Abstract

Glutamate is the major excitatory neurotransmitter in the central nervous system but has also important functions in the epidermis. It is involved in keratinocyte barrier function and in re-epithelialization processes after wounding. Recently, glutamate signalling has been suggested to be implicated in the development of melanoma. The present study examined the expression and functionality of metabotropic and ionotropic glutamate receptors on normal human melanocytes. We found that cultured melanocytes expressed the ionotropic glutamate receptors GluR2 and 4 [alpha-amino-3-hydroxy-5-methyl-4-isoxsazolepropionic acid (AMPA) receptors] and N-methyl-d-aspartate (NMDA) receptors 2A and 2C and possibly the metabotropic glutamate receptor 1. Melanocytes were also found to express specific glutamate transporters and decarboxylases, but appeared neither to produce nor to release l-glutamate. Stimulation with 10 or 100 microM AMPA or NMDA elevated intracellular calcium concentrations in melanocytes, and thus demonstrated the functionality of the glutamate receptors. Millimolar concentrations of l-glutamate did not induce melanocyte toxicity and had no stimulating effect on melanin production. However, blockage of AMPA and NMDA receptors with CFM-2, memantine or MK801 caused a rapid and reversible change in melanocyte morphology, which was associated with disorganisation of actin and tubulin microfilaments. After 24 h of treatment with the AMPA receptor inhibitor CFM-2, there was a sharp reduction in the expression of the crucial melanocyte differentiation and proliferation factor MiTF. The results of this study demonstrate a role for glutamate in melanocyte regulation that may have implications in melanocyte associated disorders.

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  • Glutamate signaling genes are widely expressed in tissues beyond the CNS, including osteoblasts, osteoclasts, melanocytes, and chondrocytes.

    “Glutamate signaling genes are also widely expressed in tissues beyond the CNS, including osteoblasts, osteoclasts, melanocytes, and chondrocytes (Wang et al., 2005;Hoogduijn et al., 2006;Devi et al., 2013;Julio-Pieper et al., 2011;Matta, 2013).”

    From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Hoogduijn et al., 2006

  • Some evidence for direct effects of glutamate signaling derives from the fact that glutamate receptor, transporter, and other signaling genes identified in different domestication studies are expressed in melanocytes, osteoblasts, osteoclasts, chondrocytes, and other tissues beyond the CNS.

    “Some evidence for this derives from the fact that glutamate receptor, transporter, and other signaling genes identified in different domestication studies are expressed in melanocytes, osteoblasts, osteoclasts, chondrocytes, and other tissues beyond the CNS (Wang et al., 2005;Hoogduijn et al., 2006;Devi et al., 2013;Julio-Pieper et al., 2011;Matta, 2013).”

    From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Hoogduijn et al., 2006

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Authors
Hoogduijn, M. J., Hitchcock, I. S., Smit, N. P. M., Gillbro, J. M., Schallreuter, K. U., & Genever, P. G.
Affiliations
  • University of York (GB)
  • University of California San Diego (US)
  • Leiden University Medical Center (NL)
  • University of Bradford (GB)
Corresponding author
Hoogduijn, M. J.
ORCID
Venue
Pigment Cell Research
Publisher
Wiley
Published
2005-11-10
Volume
19
Issue
1
Pages
58-67
ISSN
  • 0893-5785 (ISSN-L)
  • 1600-0749
DOI
10.1111/j.1600-0749.2005.00284.x
OpenAlex
W2133617951
Cited by
47
References
34
Citations by year
2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 3 · 2012: 6
FWCI
0.68
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Pigment Cell Research (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords
glutamate receptors, melanocytes, MITF, AMPA receptors, NMDA receptor, metabotropic glutamate receptor 1, glutamate transporters, intracellular calcium, melanocyte differentiation, melanoma, melanocyte morphology
MeSH terms
Benzodiazepinones, Cells, Cultured, Gene Expression Regulation, Humans, Melanocytes, Memantine, Molecular Sequence Data, Dizocilpine Maleate, Apoptosis, Receptors, Glutamate, Excitatory Amino Acid Antagonists, Glutamic Acid, Protein Isoforms, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Cell Shape, Microphthalmia-Associated Transcription Factor

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