title: Antiallergic effect of epinastine (WAL 801 CL) on immediate hypersensitivity reactions: (I). Elucidation of the mechanism for histamine release inhibition.
abstract: Epinastine caused an inhibition of histamine release from rat peritoneal mast cells induced by both antigen-antibody reaction and compound 48/80. Epinastine was similarly effective in inhibiting compound 48/80-induced histamine release not only from isolated rat peritoneal mast cells but also from rat mesenterial pieces. Also, histamine release from lung pieces obtained from actively sensitized guinea pigs after exposure to antigen challenge was markedly inhibited by epinastine. The drug was effective in inhibiting not only Ca2+ uptake into lung mast cells in actively sensitized guinea pigs but also Ca2+ release from the intracellular Ca store of rat peritoneal mast cells exposed to both compound 48/80 and substance P. No significant changes were observed in phosphodiesterase activity in rat peritoneal mast cells treated with epinastine, while adenylate cyclase activity was augmented by epinastine. Epinastine has no inhibitory effect on histamine release induced by Ca2+ or IP3 from permeabilized mast cells. However, the drug significantly and dose-dependently suppressed calmodulin activity suggesting that histamine release inhibition due to epinastine may be partly attributable to Ca(2+)-calmodulin dependent process(es). The drug caused no visible changes in thermodynamic behavior of lipids, either in order parameter or in differential scanning calorimetry, indicating that the drug has no influence on membrane fluidity.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Kamei
authors.forename: M
authors.initials: M
authors.lastname: Akagi
authors.forename: M
authors.initials: M
authors.lastname: Mio
authors.forename: K
authors.initials: K
authors.lastname: Kitazumi
authors.forename: K
authors.initials: K
authors.lastname: Izushi
authors.forename: S
authors.initials: S
authors.lastname: Masaki
authors.forename: K
authors.initials: K
authors.lastname: Tasaka
mesh_terms: D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology*; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D008051:Lipid Bilayers; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D008051:Lipid Bilayers; D003189:p-Methoxy-N-methylphenethylamine; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; C053090:epinastine; D002118:Calcium