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首页> 外文期刊>Pigment cell research >Glutamate receptors on human melanocytes regulate the expression of MiTF
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Glutamate receptors on human melanocytes regulate the expression of MiTF

机译：人黑素细胞上的谷氨酸受体调节MiTF的表达

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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.
机译：谷氨酸是中枢神经系统中主要的兴奋性神经递质，但在表皮中也具有重要功能。它涉及角质形成细胞屏障功能和受伤后的再上皮形成过程。最近，已经暗示谷氨酸信号传导与黑色素瘤的发展有关。本研究检查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了离子型谷氨酸受体GluR2和4 [α-氨基-3-羟基-5-甲基-4-异恶唑唑丙酸（AMPA）受体]和N-甲基-D-天冬氨酸（NMDA）受体2A和2C黑色素细胞也被发现表达特定的谷氨酸转运蛋白和脱羧酶，但既不产生也不释放L-谷氨酸。用10或100μMAMPA或NMDA刺激可提高黑素细胞中的细胞内钙浓度，因此证明了谷氨酸受体的功能。毫摩尔浓度的L-谷氨酸不引起黑素细胞毒性，对黑素的产生没有刺激作用。但是，用CFM-2，美金刚或MK801阻断AMPA和NMDA受体会导致黑色素细胞形态发生快速且可逆的变化，这与肌动蛋白和微管蛋白微丝的混乱有关。用AMPA受体抑制剂CFM-2治疗24小时后，关键的黑素细胞分化和增殖因子MiTF的表达急剧下降。这项研究的结果证明了谷氨酸在黑色素细胞调节中的作用，这可能与黑色素细胞相关的疾病有关。

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