title: Azelastine's inhibition of histamine and tryptase release from human umbilical cord blood-derived cultured mast cells as well as rat skin mast cell-induced vascular permeability: comparison with olopatadine.
abstract: Mast cells are involved in early and late-phase reactions by releasing vasoactive molecules, proteases, and cytokines. Azelastine and olopatadine are histamine 1 receptor (H-1R) antagonists with antiallergic effects present in the ophthalmic solutions Optivar and Patanol, respectively. Because it is difficult to obtain animal or human conjunctival tissue, we first investigated the effect of these compounds on histamine and tryptase release from cultured human mast cells (CHMCs) grown out of human umbilical cord blood-derived CD34+ cells. Sensitized CHMCs were pretreated with various concentrations of azelastine or olopatadine for 5 minutes. Then, CHMCs were challenged with anti-immunoglobulin E (IgE) and the released mediators were quantitated. The greatest inhibition of mediator release was seen when CHMCs were pretreated with 24 microM of azelastine or 133 microM of olopatadine (2% dilution of azelastine or 5% olopatadine original ophthalmic solutions, respectively). We then studied the drug concentrations that gave optimal results on skin vasodilation induced by the mast cell secretagogue compound 48/80. An intradermal injection of 48/80 in rats, to which Evan's blue had been administered via the tail vein, induced substantial dye extravasation. Pretreatment of the injection site for 5 minutes with either 24 microM of azelastine or 133 microM of olopatadine completely prevented extravasation; this effect was quantitated also by fluorometric assessment of Evan's blue extracted in formamide. Evaluation of skin mast cells from injected sites showed that mast cell degranulation was inhibited greatly. These results indicate that on an equimolar basis, azelastine was a more potent inhibitor than olopatadine of both CHMC and rat skin mast cells activation.
authors.affiliation: Departments of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and New England Medical Center, Boston, Massachusetts, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lytinas
authors.forename: Duraisamy
authors.initials: D
authors.lastname: Kempuraj
authors.forename: Man
authors.initials: M
authors.lastname: Huang
authors.forename: Kristiana
authors.initials: K
authors.lastname: Kandere
authors.forename: William
authors.initials: W
authors.lastname: Boucher
authors.forename: Richard
authors.initials: R
authors.lastname: Letourneau
authors.forename: Sheila
authors.initials: S
authors.lastname: Jeudy
authors.forename: Kim
authors.initials: K
authors.lastname: Fitzgerald
authors.forename: Kathleen
authors.initials: K
authors.lastname: Spear
authors.forename: Achilles
authors.initials: A
authors.lastname: Athanasiou
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D003990:Dibenzoxepins / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005312:Fetal Blood / Q000187:drug effects* / Q000276:immunology; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D000069605:Olopatadine Hydrochloride; D010793:Phthalazines / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000276:immunology*; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D053802:Tryptases
chemical_list: D018926:Anti-Allergic Agents; D003990:Dibenzoxepins; D018836:Inflammation Mediators; D010793:Phthalazines; D000069605:Olopatadine Hydrochloride; D012697:Serine Endopeptidases; C509223:Tpsab1 protein, rat; C509221:Tpsb2 protein, rat; D053802:Tryptases; C020976:azelastine