title: Participation of proteinase-activated receptor-2 in passive cutaneous anaphylaxis-induced scratching behavior and the inhibitory effect of tacrolimus.
abstract: Proteinase-activated receptor-2 (PAR2) may be an important regulator of skin mast cell function during cutaneous inflammation and hypersensitivity. However, little is known of the role of PAR2 in allergic pruritus, because mast cells, which are thought to be responsible for this symptom, can release a number of different pruritogens. In the present study, we investigated the effects of several agents on passive cutaneous anaphylaxis-induced scratching behavior in ICR mice. As a result, cetirizine and ketanserin produced dose-dependent inhibition of scratching behavior induced by passive cutaneous anaphylaxis. Combined cetirizine with ketanserin exhibited significant inhibitory effects for the number of passive cutaneous anaphylaxis-induced scratching behavior. Pretreatment of the experimental animals with PAR2-neutralizing antibody and protease inhibitor leupeptin significantly inhibited passive cutaneous anaphylaxis-induced scratching behavior. Furthermore, we found that topical application of tacrolimus significantly reduced the number of scratching behavior induced by passive cutaneous anaphylaxis in a dose-dependent manner. Combined cetirizine with tacrolimus also exhibited significant inhibitory effects for the number of passive cutaneous anaphylaxis-induced scratching behavior. Tacrolimus in doses of 3% and 10% significantly inhibited tryptase-induced scratching behavior. These results suggest that PAR2 may be involved in passive cutaneous anaphylaxis-induced scratching behavior and tacrolimus produces an anti-allergic pruritus effect in ICR mice.
authors: Department of Pharmacy, Changhai Hospital, the Second Military Medical University.
authors: Yu
authors: Y
authors: Zhu
authors: Cheng
authors: C
authors: Peng
authors: Jian Guo
authors: JG
authors: Xu
authors: Yan Xia
authors: YX
authors: Liu
authors: Quan Gang
authors: QG
authors: Zhu
authors: Ji Yong
authors: JY
authors: Liu
authors: Feng Qian
authors: FQ
authors: Li
authors: Jian Hua
authors: JH
authors: Wu
authors: Jin Hong
authors: JH
authors: Hu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000982:Antipruritics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D017332:Cetirizine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects* / Q000276:immunology; D011537:Pruritus / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors* / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D000982:Antipruritics; D044464:Receptor, PAR-2; D007650:Ketanserin; D016559:Tacrolimus; D017332:Cetirizine