Kazama Itsuro, Saito Kazutomo, Baba Asuka, Mori Tomohiro, Abe Nozomu, Endo Yasuhiro, Toyama Hiroaki, Ejima Yutaka, Matsubara Mitsunobu, Yamauchi Masanori
Chemotherapy. 2016;61(6):295-303. doi: 10.1159/000445023. Epub 2016 Apr 19.
Macrolides, such as clarithromycin, have antiallergic properties. Since exocytosis in mast cells is detected electrophysiologically via changes in membrane capacitance (Cm), the absence of such changes due to the drug indicates its mast cell-stabilizing effect.
Employing the whole-cell patch clamp technique in rat peritoneal mast cells, we examined the effects of clarithromycin on Cm during exocytosis. Using a water-soluble fluorescent dye, we also examined its effect on deformation of the plasma membrane.
Clarithromycin (10 and 100 μM) significantly inhibited degranulation from mast cells and almost totally suppressed the GTP-x03B3;-S-induced increase in Cm. It washed out the trapping of the dye on the surface of mast cells.
This study provides for the first time electrophysiological evidence that clarithromycin dose-dependently inhibits the process of exocytosis. The mast cell-stabilizing action of clarithromycin may be attributable to its counteractive effect on plasma membrane deformation induced by exocytosis.
大环内酯类药物，如克拉霉素，具有抗过敏特性。由于肥大细胞中的胞吐作用可通过膜电容（Cm）的变化进行电生理检测，药物导致此类变化的缺失表明其具有肥大细胞稳定作用。
在大鼠腹膜肥大细胞中采用全细胞膜片钳技术，我们检测了克拉霉素在胞吐过程中对Cm的影响。使用水溶性荧光染料，我们还检测了其对质膜变形的影响。
克拉霉素（10和100μM）显著抑制肥大细胞脱颗粒，并几乎完全抑制GTP-γ-S诱导的Cm增加。它消除了染料在肥大细胞表面的滞留。
本研究首次提供了电生理证据，表明克拉霉素剂量依赖性地抑制胞吐过程。克拉霉素的肥大细胞稳定作用可能归因于其对外吐作用诱导的质膜变形的拮抗作用。
