Effects of topical application of tacrolimus on acute itch-associated responses in mice.
Using mice, we examined whether the topical application of tacrolimus would produce an acute anti-pruritic effect. An itch-related response, scratching, was elicited by intradermal injections of mosquito allergen (10 microg/site) in sensitized mice and SLIGRL-NH2 (protease-activated receptor-2 agonist, 50 nmol/site), histamine (100 nmol/site), serotonin (100 nmol/site) and substance P (100 nmol/site) in naive ones. Topical application of 1%, but neither 0.1% nor 0.3%, tacrolimus to the skin 1 h before injection inhibited scratching induced by mosquito allergen and SLIGRL-NH2, without effects on scratching induced by histamine, serotonin, and substance P. Topical tacrolimus also inhibited licking induced by an intraplantar injection of capsaicin (0.1 microg/site). These results suggest that topical tacrolimus exerts acute inhibitory effects on allergic and protease-activated receptor-2-mediated itching. Though precise mechanisms remain unclear, the action on sensory neurons expressing protease-activated receptor-2 and transient receptor potential vanilloid-1 capsaicin receptor may be involved in the inhibitory effects of tacrolimus.
Nakano
Tasuku
T
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Andoh
Tsugunobu
T
Tayama
Manabu
M
Kosaka
Mayumi
M
Lee
Jung-Bum
JB
Kuraishi
Yasushi
Y
D000287:Administration, Topical; D000330:Aedes; D000818:Animals; D000982:Antipruritics; D001522:Behavior, Animal; D002211:Capsaicin; D005260:Female; D006632:Histamine; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology*; D012701:Serotonin; D013373:Substance P; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology*
D000982:Antipruritics; D007166:Immunosuppressive Agents; D012701:Serotonin; D013373:Substance P; D006632:Histamine; D002211:Capsaicin; D016559:Tacrolimus