Denda Mitsuhiro, Inoue Kaori, Inomata Shinji, Denda Sumiko
Shiseido Research Center, Fukuura, Kanazawa-ku, Yokohama, Japan.
J Invest Dermatol. 2002 Nov;119(5):1041-7. doi: 10.1046/j.1523-1747.2002.19504.x.
gamma-Aminobutyric acid, is an amino acid transmitter, which mediates rapid inhibition in the central nervous system. gamma-Aminobutyric acid (A) receptor is a ligand-gated chloride ion channel playing an important part in polarizing the cell membrane and reducing neuronal excitability in the neuron. In this study, we demonstrated the effects of gamma-aminobutyric acid (A) receptor agonists on the cutaneous barrier repair process after the barrier disruption of hairless mice. Topical application of gamma-aminobutyric acid and gamma-aminobutyric acid (A) receptor-specific agonists, musimol and isoguvacine, after barrier disruption accelerated the barrier recovery. The gamma-aminobutyric acid (B)-specific agonist, baclofen, did not affect the barrier recovery rate. The effect of gamma-aminobutyric acid on the barrier recovery was blocked by the gamma-aminobutyric acid (A)-receptor antagonist, bicuculline methobromide, but gamma-aminobutyric acid (B) receptor antagonist, saclofen, did not affect the effect of gamma-aminobutyric acid. Topical application of gamma-aminobutyric acid also prevented epidermal hyperplasia, which was induced by the barrier insults under low environmental humidity and bicuculline methobromide blocked the effect of gamma-aminobutyric acid on the epidermal hyperplasia. Immunoreactivity against gamma-aminobutyric acid (A) polyclonal antibody was observed in hairless mouse epidermis. The fluorescent probe of gamma-aminobutyric acid (A) receptor, TXR-musimol showed the localization of gamma-aminobutyric acid (A) receptor in the epidermis of the hairless mice. Elevation of intracellular chloride ion was induced by gamma-aminobutyric acid in cultured human keratinocytes and it was blocked by bicuculline methobromide. These results suggest that the gamma-aminobutyric acid (A)-like receptor is associated with skin barrier homeostasis and regulation of the receptor clinically effective for barrier dysfunctional or epidermal hyperproliferative diseases.
γ-氨基丁酸是一种氨基酸递质，介导中枢神经系统的快速抑制作用。γ-氨基丁酸（A）受体是一种配体门控氯离子通道，在神经元细胞膜极化和降低神经元兴奋性方面发挥重要作用。在本研究中，我们证明了γ-氨基丁酸（A）受体激动剂对无毛小鼠屏障破坏后皮肤屏障修复过程的影响。屏障破坏后局部应用γ-氨基丁酸以及γ-氨基丁酸（A）受体特异性激动剂、蝇蕈醇和异鹅膏蕈氨酸可加速屏障恢复。γ-氨基丁酸（B）特异性激动剂巴氯芬不影响屏障恢复率。γ-氨基丁酸（A）受体拮抗剂甲溴东莨菪碱可阻断γ-氨基丁酸对屏障恢复的作用，但γ-氨基丁酸（B）受体拮抗剂沙氯芬不影响γ-氨基丁酸的作用。局部应用γ-氨基丁酸还可预防低环境湿度下屏障损伤诱导的表皮增生，甲溴东莨菪碱可阻断γ-氨基丁酸对表皮增生的作用。在无毛小鼠表皮中观察到针对γ-氨基丁酸（A）多克隆抗体的免疫反应性。γ-氨基丁酸（A）受体的荧光探针TXR-蝇蕈醇显示γ-氨基丁酸（A）受体在无毛小鼠表皮中的定位。γ-氨基丁酸可诱导培养的人角质形成细胞内氯离子浓度升高，甲溴东莨菪碱可阻断该作用。这些结果表明，γ-氨基丁酸（A）样受体与皮肤屏障稳态相关，该受体的调节对屏障功能障碍或表皮过度增殖性疾病具有临床疗效。
