NMDA-type glutamate receptor is associated with cutaneous barrier homeostasis
NMDA-type glutamate receptor is associated with cutaneous barrier homeostasis
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DOI：
10.1046/j.1523-1747.2003.12238.x
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发表时间：
2003-06-01
影响因子：
6.5
通讯作者：
Denda, M
中科院分区：
文献类型：
--
作者：
Fuziwara, S;Inoue, K;Denda, M
谷氨酸受体在中枢神经系统的兴奋性突触活动中起重要作用。本研究利用无毛小鼠研究了谷氨酸受体激动剂和拮抗剂对皮肤屏障稳态的影响。局部应用L-谷氨酸、L-天冬氨酸（非特异性谷氨酸受体激动剂）和N-甲基-D-天冬氨酸（NMDA，NMDA型受体激动剂）延迟了胶带剥离破坏屏障后的屏障恢复率。另一方面，局部应用D-谷氨酸（谷氨酸受体的非特异性拮抗剂）、MK 801和D-AP 5（NMDA型受体拮抗剂）加速屏障修复。非NMDA型受体激动剂α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）不影响屏障恢复。MK-801的局部应用也促进了低环境湿度下丙酮处理诱导的表皮增生的愈合。在皮肤器官培养的屏障破坏后，立即从皮肤分泌谷氨酸显著增加。免疫组化、逆转录聚合酶链反应（RT-PCR）和原位杂交结果显示，NMDA受体样蛋白在无毛小鼠表皮表达。NMDA增加细胞间钙在培养的人角质形成细胞和增加被MK 801阻断。这些结果表明，谷氨酸起着重要的作用，作为一个信号的皮肤屏障稳态和表皮增生的屏障破坏引起的。
Glutamate receptors play an important role in the excitatory synaptic action of the central nervous system. In this study, effects of glutamate receptor agonists and antagonists on skin barrier homeostasis were studied using hairless mouse. Topical application of L-glutamic acid, L-aspartic acid (non-specific glutamate receptor agonists) and N-methyl-D-aspartate (NMDA, NMDA type receptor agonist) delayed the barrier recovery rate after barrier disruption with tape stripping. On the other hand, topical application of D-glutamic acid (non-specific antagonist of glutamate receptor), MK 801 and D-AP5, (NMDA-type receptor antagonists) accelerated the barrier repair. The non-NMDA type receptor agonist, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), did not affect the barrier recovery. Topical application of MK-801 also promoted the healing of epidermal hyperplasia induced by acetone treatment under low environmental humidity. Immediately after barrier disruption on skin organ culture, secretion of glutamic acid from skin was significantly increased. Immunohistochemistry, reverse transcription polymearse chain reaction (RT-PCR) and in situ hybridization showed an expression of NMDA-type receptor-like protein on hairless mouse epidermis. NMDA increased intercellular calcium in cultured human keratinocytes and the increase was blocked by MK 801. These results suggest that glutamate plays an important role as a signal of cutaneous barrier homeostasis and epidermal hyperplasia induced by barrier disruption.