Inhibitory effects of antipsychotic and anxiolytic agents on stress-induced degranulation of mouse dermal mast cells

Shimoda, Tomohiro; Zai-fu, Liang; Suzuki, Hidenori; Kawana, Seiji

doi:10.1111/j.1365-2230.2009.03650.x

Cited by 32 publications

(20 citation statements)

References 24 publications

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“…Bright-field images were acquired from randomly selected 0.1-mm 2 fields of view (10 views from 6 of each condition), as described in our previous studies [9,14]. Degranulated mast cells were defined as cells associated with ≥ 8 granules outside the cell membrane, as described previously [15]. These mast cells were then counted and their ratio to all mast cells was calculated.…”

Section: Methodsmentioning

confidence: 99%

Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

Baba¹,

Tachi²,

Maruyama³

et al. 2015

Cell Physiol Biochem

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Backgroud/Aims: Besides its anti-allergic properties as a histamine receptor antagonist, olopatadine stabilizes mast cells by inhibiting the release of chemokines. Since olopatadine bears amphiphilic features and is preferentially partitioned into the lipid bilayers of the plasma membrane, it would induce some morphological changes in mast cells and thus affect the process of exocytosis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of olopatadine and other anti-allergic drugs on the membrane capacitance (Cm) in rat peritoneal mast cells during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Low concentrations of olopatadine (1 or 10 µM) did not significantly affect the GTP-γ-S-induced increase in the Cm. However, 100 µM and 1 mM olopatadine almost totally suppressed the increase in the Cm. Additionally, these doses completely washed out the trapping of the dye on the cell surface, indicating that olopatadine counteracted the membrane surface deformation induced by exocytosis. As shown by electron microscopy, olopatadine generated inward membrane bending in mast cells. Conclusion: This study provides electrophysiological evidence for the first time that olopatadine dose-dependently inhibits the process of exocytosis in rat peritoneal mast cells. Such mast cell stabilizing properties of olopatadine may be attributed to its counteracting effects on the plasma membrane deformation in degranulating mast cells.

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Section: Methodsmentioning

confidence: 99%

Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

Baba¹,

Tachi²,

Maruyama³

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

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“…Bright-field images were acquired from randomly selected 0.1-mm 2 fields of view (10 views from 6 of each condition), as described in our previous study [23]. Degranulated mast cells were defined as cells associated with ≥ 8 granules outside the cell membrane as described previously [13]. These mast cells were then counted and their ratio to all mast cells was calculated.…”

Section: Methodsmentioning

confidence: 99%

“…However, in some situations, such as in food-dependent exercise-induced anaphylaxis (FDEIA) [7,8], salicylate and its acetyl derivative, aspirin, can stimulate chemokine release from mast cells, triggering adverse immunological reactions [9,10]. On the other hand, chlorpromazine, one of the most traditionally used antipsychotic drugs [11], has also been recognized as an anti-allergic agent, because it inhibits histamine release from mast cells [12,13]. Concerning the mechanisms by which these drugs exert their effects, the studies indicate that the drug-induced changes in the intracellular Ca 2+ concentration ([Ca 2+ ] i ) are primarily responsible [9,12].…”

Section: Introductionmentioning

confidence: 99%

Amphipaths Differentially Modulate Membrane Surface Deformation in Rat Peritoneal Mast Cells During Exocytosis

Kazama

Maruyama²,

Takahashi³

et al. 2013

Cell Physiol Biochem

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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. Methods: 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. Results: 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. Conclusion: 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.

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“…By measuring the amount of chemical mediators released from mast cells, previous studies have indirectly determined the mast cell-stabilizing properties of drugs [20,39,40,41]. However, besides their exocytotic release of chemical mediators, such as histamine, serotonin, prostaglandins, and leukotrienes, mast cells produce numerous kinds of inflammatory cytokines and growth factors, including interleukins, tumor necrosis factors, and vascular endothelial or fibroblast growth factors [42].…”

Section: Discussionmentioning

confidence: 99%

“…Bright-field images were acquired from randomly selected 0.1-mm 2 fields of view (10 views from 6 of each condition) as described in our previous studies [17,18,19]. Degranulated mast cells were defined as cells associated with ≥8 granules outside of the cell membrane as described previously [17,18,19,20]. These mast cells were then counted and their ratio to all mast cells was calculated.…”

Section: Methodsmentioning

confidence: 99%

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

Kazama¹,

Saito²,

Baba³

et al. 2016

Chemotherapy

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Background: 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. Methods: 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. Results: Clarithromycin (10 and 100 μM) significantly inhibited degranulation from mast cells and almost totally suppressed the GTP-γ-S-induced increase in Cm. It washed out the trapping of the dye on the surface of mast cells. Conclusions: 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.

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Inhibitory effects of antipsychotic and anxiolytic agents on stress-induced degranulation of mouse dermal mast cells

Abstract: Antipsychotic and anxiolytic agents may be effective treatments for stress-aggravated inflammatory skin diseases by inhibition of mast-cell degranulation.

Cited by 32 publications

References 24 publications

Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

Amphipaths Differentially Modulate Membrane Surface Deformation in Rat Peritoneal Mast Cells During Exocytosis

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

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