Denda Mitsuhiro, Inoue Kaori, Fuziwara Shigeyoshi, Denda Sumiko
Shiseido Research Center, 2-12-1 Fukuura, Kanazawa-ku, Yokohama, Japan.
J Invest Dermatol. 2002 Nov;119(5):1034-40. doi: 10.1046/j.1523-1747.2002.19505.x.
The effects of ATP receptor agonists/antagonists on skin barrier recovery rate were evaluated in hairless mice. Topical application of ATP and alpha,beta-methylene ATP (agonist of P2X receptor) delayed barrier recovery. Topical application of suramin (nonspecific ATP receptor antagonist), pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) (P2X receptor antagonist), and 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP) (P2X1, P2X3, P2X2/3 antagonist) after barrier disruption accelerated the barrier repair. The P2Y type receptor antagonist Reactive Blue 2 did not affect the barrier repair process. Moreover, topical application of TNP-ATP prevented epidermal hyperplasia induced by barrier insult under low environmental humidity. ATP was secreted immediately after tape stripping on skin in organ culture. alpha,beta-Methylene ATP increased intercellular calcium in cultured keratinocytes and the increase was blocked by TNP-ATP. Both reverse transcription polymerase chain reaction assay and immunohistochemical study showed the existence of protein that had a structure similar to P2X3 on hairless mouse epidermis. These results suggest that cutaneous barrier homeostasis can be regulated by cation flux through a P2X3-like ATP receptor.
在无毛小鼠中评估了ATP受体激动剂/拮抗剂对皮肤屏障恢复率的影响。局部应用ATP和α,β-亚甲基ATP（P2X受体激动剂）会延迟屏障恢复。屏障破坏后局部应用苏拉明（非特异性ATP受体拮抗剂）、磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸（PPADS）（P2X受体拮抗剂）和2',3'-O-（2,4,6-三硝基苯基）三磷酸腺苷（TNP-ATP）（P2X1、P2X3、P2X2/3拮抗剂）可加速屏障修复。P2Y型受体拮抗剂活性蓝2不影响屏障修复过程。此外，在低环境湿度下，局部应用TNP-ATP可预防屏障损伤诱导的表皮增生。在器官培养中，胶带剥离皮肤后ATP立即分泌。α,β-亚甲基ATP增加了培养角质形成细胞中的细胞间钙，且该增加被TNP-ATP阻断。逆转录聚合酶链反应分析和免疫组织化学研究均显示无毛小鼠表皮上存在结构类似于P2X3的蛋白质。这些结果表明，阳离子通过类似P2X3的ATP受体流动可调节皮肤屏障的稳态。
