Enoki Eisuke, Sada Kiyonao, Qu Xiujuan, Kyo Shinkou, Miah S M Shahjahan, Hatani Tomoko, Tomoda Akio, Yamamura Hirohei
Division of Proteomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Japan.
J Pharmacol Sci. 2004 Mar;94(3):329-33. doi: 10.1254/jphs.94.329.
Antigen-induced aggregation of the high affinity IgE receptor (FcepsilonRI) on mast cells induces degranulation to release chemical mediators, leading to acute allergic inflammation. We have demonstrated that the treatment of rat mast cells, RBL-2H3, with a phenoxazine derivative Phx-1 (2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one) suppresses the antigen-induced degranulation. Biochemical analysis reveals that the complementary signaling pathway through Gab2 and Akt is inhibited by this compound in mast cells. These findings suggest that phenoxazine derivatives may have a therapeutic potential for allergic diseases by inhibiting mast cell degranulation.
抗原诱导肥大细胞上高亲和力IgE受体（FcepsilonRI）聚集，会引发脱颗粒以释放化学介质，从而导致急性过敏性炎症。我们已经证明，用一种吩恶嗪衍生物Phx-1（2-氨基-4,4α-二氢-4α,7-二甲基-3H-吩恶嗪-3-酮）处理大鼠肥大细胞RBL-2H3，可抑制抗原诱导的脱颗粒。生化分析表明，该化合物在肥大细胞中抑制了通过Gab2和Akt的互补信号通路。这些发现表明，吩恶嗪衍生物可能通过抑制肥大细胞脱颗粒而具有治疗过敏性疾病的潜力。
