Participation of chemical mediators in the development of experimental allergic conjunctivitis in rats.
In the present study, we investigated the participation of chemical mediators in the development of experimental allergic conjunctivitis in rats. Cetirizine (a histamine H1 receptor antagonist), ramatroban (a thromboxane A2 (TXA2) receptor antagonist) and zafirlukast (a cysteinyl leukotrienes (cys-LTs) receptor antagonist) were orally administered from day 14 to day 42 during repeated topical antigen challenge. An increase in reactivity to antigen- and histamine-induced eye scratching behavior was observed by topical sensitization in sensitized rats. Although increased reactivity to antigen was not influenced by cetirizine, ramatoroban and zafirlukast, increased reactivity to histamine was significantly inhibited by ramatroban. The development of conjunctival edema was also observed for topical sensitization. Cetirizine caused no inhibition of the development of conjunctival edema, but ramatroban and zafirlukast inhibited the development of conjunctival edema. In addition, the number of eosinophils in the conjunctiva was increased by topical sensitization. Cetirizine had no significant effect on the increase in the number of eosinophils. However, ramatroban and zafirlukast were effective in inhibiting an increase in the number of eosinophils induced by topical sensitization. These results indicate that TXA2 is involved in increased histamine reactivity, and TXA2 and cys-LTs are associated with not only the conjunctival edema but also eosinophil infiltration during the development of experimental allergic conjunctivitis in rats.
Minami
Kazuhisa
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Tushima-naka 1-1-1, Okayama 700-8530, Japan.
Fujii
Yoko
Y
Kamei
Chiaki
C
D000284:Administration, Oral; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology; D017332:Cetirizine / Q000008:administration & dosage / Q000494:pharmacology; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D048448:Phenylcarbamates; D011537:Pruritus / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D011970:Receptors, Histamine H2 / Q000276:immunology* / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000276:immunology*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors / Q000276:immunology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000494:pharmacology
D002227:Carbazoles; D006635:Histamine H2 Antagonists; D007211:Indoles; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D048448:Phenylcarbamates; D011970:Receptors, Histamine H2; D018077:Receptors, Leukotriene; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013449:Sulfonamides; D014105:Tosyl Compounds; D010047:Ovalbumin; C083169:leukotriene D4 receptor; C063119:ramatroban; C062735:zafirlukast; D017332:Cetirizine