Holian A, Hamilton R, Scheule R K
Department of Internal Medicine, University of Texas Medical School, Houston 77030.
Agents Actions. 1991 Jul;33(3-4):318-25. doi: 10.1007/BF01986580.
Despite wide use of the drug cromolyn sodium, its mechanism of action remains unknown. The alveolar macrophage plays a major role in the regulation of the inflammatory responses of the lung which may contribute to asthma. Since the biochemical mechanism by which agonists stimulate the alveolar macrophage to produce superoxide anion has been described, the effects of cromolyn sodium on this process were examined. Cromolyn sodium (0.5-4 mM) reversibly blocked macrophage stimulation by formyl peptide and leukotriene B4, but not by phorbol diester and concanavalin A. Cromolyn sodium inhibition was not calcium dependent and could be reversed by increasing the dose of agonist. Cromolyn sodium did not elevate intracellular cAMP, nor did the characteristics of inhibition resemble those observed using cAMP to inhibit agonist stimulation. However, cromolyn sodium did block agonist-mediated stimulation of the phosphatidylinositol (PI) pathway. Taken together, the present results suggest that one site of action of cromolyn sodium may be at the GTP-binding protein of the PI pathway.
尽管色甘酸钠被广泛使用，但其作用机制仍不清楚。肺泡巨噬细胞在调节可能导致哮喘的肺部炎症反应中起主要作用。由于已经描述了激动剂刺激肺泡巨噬细胞产生超氧阴离子的生化机制，因此研究了色甘酸钠对该过程的影响。色甘酸钠（0.5-4 mM）可逆地阻断甲酰肽和白三烯B4对巨噬细胞的刺激，但不阻断佛波酯和伴刀豆球蛋白A的刺激。色甘酸钠的抑制作用不依赖于钙，并且可以通过增加激动剂的剂量来逆转。色甘酸钠不会升高细胞内cAMP，其抑制特性也与使用cAMP抑制激动剂刺激时观察到的不同。然而，色甘酸钠确实阻断了激动剂介导的磷脂酰肌醇（PI）途径的刺激。综上所述，目前的结果表明色甘酸钠的一个作用位点可能在PI途径的GTP结合蛋白处。
