Glutamate receptors on human melanocytes regulate the expression of MiTF
Glutamate receptors on human melanocytes regulate the expression of MiTF
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DOI：
10.1111/j.1600-0749.2005.00284.x
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发表时间：
2006-02-01
期刊：
影响因子：
--
通讯作者：
Genever, PG
中科院分区：
文献类型：
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作者：
Hoogduijn, MJ;Hitchcock, IS;Genever, PG
谷氨酸是中枢神经系统中的主要兴奋性神经递质，但在表皮中也具有重要功能。它参与角质形成细胞屏障功能和创伤后的上皮再形成过程。最近，谷氨酸信号转导已被认为与黑色素瘤的发展有关。本研究检测了正常人黑素细胞上代谢型和离子型谷氨酸受体的表达和功能。我们发现，培养的黑素细胞表达离子型谷氨酸受体GluR 2和4 [α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体]和N-甲基-D-天冬氨酸（NMDA）受体2A和2C，可能还有代谢型谷氨酸受体1。黑素细胞也被发现表达特定的谷氨酸转运蛋白和脱羧酶，但似乎既不产生也不释放L-谷氨酸。用10或100 μ M的AMPA或NMDA刺激，黑素细胞中的细胞内钙浓度升高，从而证明了谷氨酸受体的功能。毫摩尔浓度的L-谷氨酸盐不会诱导黑素细胞毒性，也不会刺激黑素的产生。然而，AMPA和NMDA受体与CFM-2，美金刚胺或MK 801的阻断引起黑素细胞形态的快速和可逆的变化，这与肌动蛋白和微管蛋白微丝的解体有关。在用AMPA受体抑制剂CFM-2处理24小时后，关键的黑素细胞分化和增殖因子MiTF的表达急剧减少。这项研究的结果表明，谷氨酸在黑素细胞调节中的作用可能与黑素细胞相关疾病有关。
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 mu M 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.