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Glutamate receptors on human melanocytes regulate the expression of MiTF

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JournalPigment cell research
DatePublished - Feb 2006
Issue number1
Volume19
Number of pages10
Pages (from-to)58-67
Original languageEnglish

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.

    Research areas

  • Apoptosis, Benzodiazepinones, Cell Shape, Cells, Cultured, Dizocilpine Maleate, Excitatory Amino Acid Antagonists, Gene Expression Profiling, Gene Expression Regulation, Glutamic Acid, Humans, Melanocytes, Memantine, Microphthalmia-Associated Transcription Factor, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Protein Isoforms, Receptors, Glutamate

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