Participation of proteinase-activated receptor-2 in passive cutaneous anaphylaxis-induced scratching behavior and the inhibitory effect of tacrolimus.
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.
Zhu
Yu
Y
Department of Pharmacy, Changhai Hospital, the Second Military Medical University.
Peng
Cheng
C
Xu
Jian Guo
JG
Liu
Yan Xia
YX
Zhu
Quan Gang
QG
Liu
Ji Yong
JY
Li
Feng Qian
FQ
Wu
Jian Hua
JH
Hu
Jin Hong
JH
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*
D000911:Antibodies, Monoclonal; D000982:Antipruritics; D044464:Receptor, PAR-2; D007650:Ketanserin; D016559:Tacrolimus; D017332:Cetirizine