神经生长因子诱导大鼠肥大细胞释放组胺的信号通路。
Signaling pathway in nerve growth factor induced histamine release from rat mast cells.
作者信息
Stempelj M, Ferjan I
机构信息
Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia.
出版信息
Inflamm Res. 2005 Aug;54(8):344-9. doi: 10.1007/s00011-005-1364-7.
OBJECTIVE AND DESIGN
We investigated a signal transduction pathway involved in NGF induced histamine secretion from mast cells. We compared this mechanism with the exocytosis induced by basic secretagogue compound 48/80.
MATERIALS AND METHODS
Isolated rat peritoneal mast cells were obtained from male Wistar rats. Histamine release was assayed spectrofluorometrically.
RESULTS
We found that tyrosine kinase inhibitor genistein, phospholipase C (PLC) inhibitor U-73122, phosphatidylinositol 3-kinase (PI-3 kinase) inhibitor wortmannin, protein kinase C (PKC) inhibitors, staurosporine and GF109203X, but not MAP kinase inhibitors, SB203580 and PD98059, reduce histamine secretion in NGF provoked mast cell degranulation. In compound 48/80 mediated degranulation, we confirmed only the involvement of tyrosine kinase and PLC, but not PI-3 kinase, PKC and MAP kinases.
CONCLUSIONS
Our results indicate that release of histamine from mast cells after stimulation with NGF is regulated by tyrosine kinase, PLC, PI-3 kinase and PKC, but not by MAP kinases. This biochemical pathway differs from that provoked by compound 48/80.
目的与设计
我们研究了一条参与神经生长因子（NGF）诱导肥大细胞分泌组胺的信号转导途径。我们将此机制与碱性促分泌剂化合物48/80诱导的胞吐作用进行了比较。
材料与方法
从雄性Wistar大鼠获取分离的大鼠腹膜肥大细胞。采用荧光分光光度法测定组胺释放。
结果
我们发现酪氨酸激酶抑制剂染料木黄酮、磷脂酶C（PLC）抑制剂U - 73122、磷脂酰肌醇3激酶（PI - 3激酶）抑制剂渥曼青霉素、蛋白激酶C（PKC）抑制剂星形孢菌素和GF109203X，但不是丝裂原活化蛋白激酶（MAP激酶）抑制剂SB203580和PD98059，可减少NGF刺激引起的肥大细胞脱颗粒过程中的组胺分泌。在化合物48/80介导的脱颗粒过程中，我们仅证实酪氨酸激酶和PLC参与其中，而PI - 3激酶、PKC和MAP激酶未参与。
结论
我们的结果表明，NGF刺激后肥大细胞释放组胺受酪氨酸激酶、PLC、PI - 3激酶和PKC调节，而不受MAP激酶调节。这条生化途径与化合物48/80引发的途径不同。
Zotero 插件