Kazama Itsuro, Maruyama Yoshio, Takahashi Sara, Kokumai Takashi
Department of Physiology I, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku, Sendai, Miyagi, Japan.
Cell Physiol Biochem. 2013;31(4-5):592-600. doi: 10.1159/000350079. Epub 2013 Apr 26.
BACKGROUND/AIMS: Salicylate and chlorpromazine exert differential effects on the chemokine release from mast cells. Since these drugs are amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membranes, they would induce some morphological changes in mast cells and thus affect the process of exocytosis.
Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate and chlorpromazine on the membrane capacitance (Cm) during exocytosis in rat peritoneal mast cells. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on plasma membrane deformation of the cells.
Salicylate dramatically accelerated the GTP-γ-S-induced increase in the Cm immediately after its application, whereas chlorpromazine significantly suppressed the increase. Treatment with salicylate increased the trapping of the dye on the cell surface, while treatment with chlorpromazine completely washed it out, indicating that both drugs induced membrane surface deformation in mast cells.
This study demonstrated for the first time that membrane amphipaths, such as salicylate and chlorpromazine, may oppositely modulate the process of exocytosis in mast cells, as detected by the changes in the Cm. The plasma membrane deformation induced by the drugs was thought to be responsible for their differential effects.
背景/目的：水杨酸盐和氯丙嗪对肥大细胞趋化因子的释放具有不同的影响。由于这些药物具有两亲性，且优先分配到质膜的脂质双层中，它们会在肥大细胞中引起一些形态变化，从而影响胞吐作用过程。
采用标准的膜片钳全细胞记录技术，我们研究了水杨酸盐和氯丙嗪对大鼠腹膜肥大细胞胞吐过程中膜电容（Cm）的影响。使用水溶性荧光染料荧光素黄进行共聚焦成像，我们还研究了它们对细胞的质膜变形的影响。
水杨酸盐在应用后立即显著加速了GTP-γ-S诱导的Cm增加，而氯丙嗪则显著抑制了这种增加。水杨酸盐处理增加了染料在细胞表面的捕获，而氯丙嗪处理则将其完全洗脱，表明这两种药物都诱导了肥大细胞的膜表面变形。
本研究首次证明，膜两亲性物质，如水杨酸盐和氯丙嗪，可能通过Cm的变化对肥大细胞的胞吐过程产生相反的调节作用。药物诱导的质膜变形被认为是其产生不同作用的原因。
