title: Olopatadine inhibits exocytosis in rat peritoneal mast cells by counteracting membrane surface deformation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Baba
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tachi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Maruyama
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; D003990:Dibenzoxepins / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D005456:Fluorescent Dyes / Q000737:chemistry; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D000069605:Olopatadine Hydrochloride; D018408:Patch-Clamp Techniques; D010537:Peritoneum / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018926:Anti-Allergic Agents; D003990:Dibenzoxepins; D005456:Fluorescent Dyes; D000069605:Olopatadine Hydrochloride