Hydrocortisone and dexamethasone dose-dependently stabilize mast cells derived from rat peritoneum
Hydrocortisone and dexamethasone dose-dependently stabilize mast cells derived from rat peritoneum
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DOI：
10.1016/j.pharep.2016.09.005
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发表时间：
2016-01-01
影响因子：
4.4
通讯作者：
Kazama, Itsuro
中科院分区：
文献类型：
--
作者：
Mori, Tomohiro;Abe, Nozomu;Kazama, Itsuro
背景：皮质类固醇药物除了具有抗炎作用外，还具有抗过敏作用。肥大细胞的胞吐是电生理学上检测到的全细胞膜电容（Cm）的增加。因此，暴露于药物后缺乏这种增加表明它们具有稳定肥大细胞的作用。方法：观察1、10、100、200 μ M氢化可的松和地塞米松对大鼠腹膜肥大细胞脱颗粒的影响。采用全细胞膜片钳记录技术，我们还测试了它们在胞吐过程中对Cm的影响。结果：在相对较低的浓度（1,10 μ M）下，氢化可的松和地塞米松对gtp - γ - s诱导的肥大细胞脱颗粒和Cm升高均无显著影响。然而，在高剂量（100,200 μ M）下，这些药物抑制肥大细胞的脱颗粒，并显著抑制gtp - γ - s诱导的Cm增加。结论：我们的研究结果首次提供了电生理学证据，证明皮质类固醇药物，如氢化可的松和地塞米松，以剂量依赖性的方式抑制肥大细胞的胞外过程。这些药物的肥大细胞稳定作用可能归因于它们的“非基因组”作用，通过这种作用，它们发挥快速的抗过敏作用。(C) 2016年由Elsevier Sp. z . o.o.代表波兰科学院药理学研究所出版。
Background: Besides their anti-inflammatory properties, corticosteroid drugs exert anti-allergic effects. Exocytosis of mast cells is electrophysiologically detected as the increase in the whole-cell membrane capacitance (Cm). Therefore, the lack of such increase after exposure to the drugs suggests their mast cell stabilizing effects.Methods: We examined the effects of 1, 10, 100 and 200 mu M hydrocortisone or dexamethasone on the degranulation from rat peritoneal mast cells. Employing the whole-cell patch-clamp recording technique, we also tested their effects on the Cm during exocytosis.Results: At relatively lower concentrations (1,10 mu M), both hydrocortisone and dexamethasone did not significantly affect the degranulation from mast cells and the increase in the Cm induced by GTP-gamma-S. Nevertheless, at higher doses (100, 200 mu M), these drugs inhibited the degranulation from mast cells and markedly suppressed the GTP-gamma-S-induced increase in the Cm.Conclusions: Our results provided electrophysiological evidence for the first time that corticosteroid drugs, such as hydrocortisone and dexamethasone, inhibited the exocytotic process of mast cells in a dose-dependent manner. The mast cell-stabilizing effects of these drugs may be attributable to their "non-genomic" action, by which they exert rapid anti-allergic effects. (C) 2016 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.