title: Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties.
abstract: 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-x03B3;-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.
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku, Sendai, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Baba
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tachi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ejima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Endo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Toyama
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Matsubara
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Saito
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Chieko
authors.initials: C
authors.lastname: Miura
authors.forename: Itsuro
authors.initials: I
authors.lastname: Kazama
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005089:Exocytosis / Q000187:drug effects; D007665:Ketotifen / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010537:Peritoneum / Q000166:cytology / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D018926:Anti-Allergic Agents; D062367:ortho-Aminobenzoates; C012293:tranilast; D007665:Ketotifen