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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-19
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0893-5785
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
58-67
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16420247-Apoptosis, pubmed-meshheading:16420247-Benzodiazepinones, pubmed-meshheading:16420247-Cell Shape, pubmed-meshheading:16420247-Cells, Cultured, pubmed-meshheading:16420247-Dizocilpine Maleate, pubmed-meshheading:16420247-Excitatory Amino Acid Antagonists, pubmed-meshheading:16420247-Gene Expression Profiling, pubmed-meshheading:16420247-Gene Expression Regulation, pubmed-meshheading:16420247-Glutamic Acid, pubmed-meshheading:16420247-Humans, pubmed-meshheading:16420247-Melanocytes, pubmed-meshheading:16420247-Memantine, pubmed-meshheading:16420247-Microphthalmia-Associated Transcription Factor, pubmed-meshheading:16420247-Molecular Sequence Data, pubmed-meshheading:16420247-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:16420247-Protein Isoforms, pubmed-meshheading:16420247-Receptors, Glutamate
pubmed:year
2006
pubmed:articleTitle
Glutamate receptors on human melanocytes regulate the expression of MiTF.
pubmed:affiliation
Biomedical Tissue Research Group, Department of Biology, University of York, York YO10 5YW, UK. mjh26@york.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't