Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

Chemotherapy ◽  
2016 ◽  
Vol 61 (6) ◽  
pp. 295-303 ◽  
Author(s):  
Itsuro Kazama ◽  
Kazutomo Saito ◽  
Asuka Baba ◽  
Tomohiro Mori ◽  
Nozomu Abe ◽  
...  
Keyword(s):  
Mast Cell ◽  
Plasma Membrane ◽  
Mast Cells ◽  
Water Soluble ◽  
Patch Clamp Technique ◽  
Membrane Deformation ◽  
Whole Cell Patch Clamp ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells ◽  
First Time

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.

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

2015 ◽  
Vol 35 (1) ◽  
pp. 386-396 ◽  
Author(s):  
Asuka Baba ◽  
Masahiro Tachi ◽  
Yoshio Maruyama ◽  
Itsuro Kazama
Keyword(s):  
Plasma Membrane ◽  
Mast Cells ◽  
Lipid Bilayers ◽  
Surface Deformation ◽  
Lucifer Yellow ◽  
Membrane Surface ◽  
Water Soluble ◽  
Confocal Imaging ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells

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.

scholarly journals Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

2016 ◽  
Vol 38 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Asuka Baba ◽  
Masahiro Tachi ◽  
Yutaka Ejima ◽  
Yasuhiro Endo ◽  
Hiroaki Toyama ◽  
...  
Keyword(s):  
Mast Cell ◽  
Plasma Membrane ◽  
Mast Cells ◽  
Lucifer Yellow ◽  
Water Soluble ◽  
Confocal Imaging ◽  
Whole Cell ◽  
Peritoneal Mast Cells ◽  
Cell Recording ◽  
Cell Membrane Capacitance

Background: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm), the absence of such changes by these drugs indicates their mast cell-stabilizing properties. Methods: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm 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: Relatively lower concentrations of tranilast (100, 250 µM) and ketotifen (1, 10 µM) did not significantly affect the GTP-γ-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM) and ketotifen (50, 100 µM) almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. Conclusions: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.

scholarly journals α1-Adrenergic Receptor Blockade by Prazosin Synergistically Stabilizes Rat Peritoneal Mast Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Nozomu Abe ◽  
Hiroaki Toyama ◽  
Yutaka Ejima ◽  
Kazutomo Saito ◽  
Tsutomu Tamada ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
High Dose ◽  
Patch Clamp Technique ◽  
Receptor Agonists ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells

Background. Adrenaline quickly inhibits the release of histamine from mast cells. Besides β2-adrenergic receptors, several in vitro studies also indicate the involvement of α-adrenergic receptors in the process of exocytosis. Since exocytosis in mast cells can be detected electrophysiologically by the changes in the membrane capacitance (Cm), its continuous monitoring in the presence of drugs would determine their mast cell-stabilizing properties. Methods. Employing the whole-cell patch-clamp technique in rat peritoneal mast cells, we examined the effects of adrenaline on the degranulation of mast cells and the increase in the Cm during exocytosis. We also examined the degranulation of mast cells in the presence or absence of α-adrenergic receptor agonists or antagonists. Results. Adrenaline dose-dependently suppressed the GTP-γ-S-induced increase in the Cm and inhibited the degranulation from mast cells, which was almost completely erased in the presence of butoxamine, a β2-adrenergic receptor antagonist. Among α-adrenergic receptor agonists or antagonists, high-dose prazosin, a selective α1-adrenergic receptor antagonist, significantly reduced the ratio of degranulating mast cells and suppressed the increase in the Cm. Additionally, prazosin augmented the inhibitory effects of adrenaline on the degranulation of mast cells. Conclusions. This study provided electrophysiological evidence for the first time that adrenaline dose-dependently inhibited the process of exocytosis, confirming its usefulness as a potent mast cell stabilizer. The pharmacological blockade of α1-adrenergic receptor by prazosin synergistically potentiated such mast cell-stabilizing property of adrenaline, which is primarily mediated by β2-adrenergic receptors.

PT pretreatment inhibits 48/80-induced activation of Ca(+)-permeable channels in rat peritoneal mast cells

1990 ◽  
Vol 259 (5) ◽  
pp. C715-C722 ◽  
Author(s):  
M. Kuno ◽  
J. Kawaguchi ◽  
M. Mukai ◽  
F. Nakamura
Keyword(s):  
Mast Cells ◽  
Patch Clamp ◽  
Room Temperature ◽  
Plasma Membranes ◽  
Patch Clamp Technique ◽  
Permeable Channel ◽  
Peritoneal Mast Cells ◽  
Fluorescence Change ◽  
Stimulus Secretion Coupling ◽  
Rat Peritoneal Mast Cells

We recently reported that the secretagogue, compound 48/80, activated Ca2(+)-permeable channels of mast cells possibly via a second messenger [Kuno, Okada, and Shibata. Am. J. Physiol. 256 (Cell Physiol. 25): C560-C568, 1989]. The effects of pretreatment with pertussis toxin (PT) on compound 48/80 (48/80)-induced activation of the Ca2(+)-permeable channel have now been investigated by measuring Ca2+ signals of cell suspensions using the Ca2+ indicator fura-2 and by recording Ba2+ currents through the channel using the patch-clamp technique. In the presence of extracellular Ca2+, the fluorescence change was biphasic, with an immediate rise and a delayed peak at room temperature. The delayed peak, mainly due to Ca2+ entry through plasma membranes, was greatly reduced by pretreatment with PT. The quenching of the fluorescence by 48/80-induced Mn2+ influx was also decreased by PT, whereas the Ca2+ transients due to Ca2+ release from the intracellular stores apparently did not change. In patch-clamp recordings from cell-attached patches with pipettes containing isotonic Ba2+, the 48/80-induced Ba2+ currents were either suppressed or delayed in the PT-treated cells, under conditions where degranulation was absent. These results suggest that PT-sensitive GTP-binding protein is involved in activating the Ca2(+)-permeable channel in mast cells during stimulus-secretion coupling.

Inhibition of Mast Cell-Mediated Anaphylaxis by Sochungryong-Tang

2000 ◽  
Vol 28 (01) ◽  
pp. 69-76 ◽  
Author(s):  
H. M. Kim ◽  
G. S. Yoon ◽  
J. U. Seo ◽  
G. Moon ◽  
H. R. Kim ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Anaphylactic Shock ◽  
Mast Cell Degranulation ◽  
Dependent Manner ◽  
Asian Philosophy ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells ◽  
Anti Body ◽  
Dose Dependent

According to traditional Asian philosophy, Sochungryong-Tang (S-Tang) is a prescription for treating exterior syndrome. In this study, we investigated the effect of S-Tang on mast cell-mediated anaphylaxis. S-Tang completely inhibited compound 48/80-induced systemic anaphylactic shock at a dose of 100 mg/kg. When S-Tang was given as pretreatment at concentrations ranging from 1 to 1000 mg/kg, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. S-Tang inhibited the local anaphylaxis activated by anti-dinitrophenyl (DNP) IgE anti-body, and also inhibited the histamine release from the rat peritoneal mast cells by compound 48/80 or anti-DNP IgE. These results indicate that S-Tang may contain substances with actions that inhibit mast cell degranulation.

scholarly journals Anti-immunoglobulin-induced histamine secretion by rat peritoneal mast cells studied by immunoferritin electron microscopy.

1975 ◽  
Vol 142 (2) ◽  
pp. 391-402 ◽  
Author(s):  
D Lawson ◽  
C Fewtrell ◽  
B Gomperts ◽  
M Raff
Keyword(s):  
Electron Microscopy ◽  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Histamine Secretion ◽  
Calcium Dependent ◽  
Peritoneal Mast Cells ◽  
Rat Peritoneal Mast Cells

We have used ferritin-conjugated divalent and monovalent anti-Ig antibodies to study simultaneously, histamine secretion and the ultrastructural distribution and redistribution of Ig receptors on rat peritoneal mast cells. We conclude that (a) divalent anti-Ig is required for both receptor redistribution and for calcium-dependent degranulation and histamine release, (b) divalent anti-Ig induces patching and pinocytosis but not capping of Ig molecules, (c) neither capping nor pinocytosis are required for triggering and if clustering is necessary, then less than 10 Ig molecules are required per cluster, and (d) degranulation (and histamine release) is not an all or none response of the mast cell.

scholarly journals CYTOFLUOROMETRIC STUDY OF MAST CELL POLYANIONS II. ADULT RAT PERITONEAL MAST CELLS REGENERATING AFTER POLYMYXIN TREATMENT

1969 ◽  
Vol 17 (1) ◽  
pp. 56-61 ◽  
Author(s):  
SAM L. MEYER ◽  
ALEX M. SAUNDERS
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Polymyxin B ◽  
Adult Rat ◽  
Peritoneal Mast Cells ◽  
Fetal Rats ◽  
Rat Peritoneal Mast Cells ◽  
Time Changes ◽  
Metachromatic Granules ◽  
And Storage

Mast cells with metachromatic granules are not detectable in rats after polymyxin-B sulfate treatment. The morphologic and staining characteristics of the cells that repopulate the peritoneal cavity resemble those of mast cells of fetal rats in their maturation sequence, except that, in the adult, the sequence requires at least 56 days. During this time changes occur in the competitive staining of mast cells with acridine orange-sodium chloride, indicating that polyanion synthesis and storage in the granules is a multiphasic phenomenon.

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