PMID- 19818345
OWN - NLM
STAT- MEDLINE
DCOM- 20100217
LR  - 20131121
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 626
IP  - 2-3
DP  - 2010 Jan 25
TI  - Depletion of substance P, a mechanism for inhibition of mouse scratching behavior 
      by tacrolimus.
PG  - 283-9
LID - 10.1016/j.ejphar.2009.09.043 [doi]
AB  - Itching is the most important problem in atopic dermatitis and tacrolimus has 
      been suggested to attenuate the itching by topical application. However, the 
      anti-itch mechanism of tacrolimus has not been well elucidated. In the present 
      study, an allergic dermatitis accompanied by frequent scratching behaviors was 
      induced by repeated paintings with 2,4-dinitrofluorobenzene (DNFB) acetone 
      solution onto the mouse ear and the effects of tacrolimus and dexamethasone on 
      the dermatitis and associated scratching behavior were comparatively examined. 
      Repeated DNFB paintings caused a typical dermatitis accompanied by elevated serum 
      immunoglobulin E (IgE) and frequent scratching behaviors. Both tacrolimus and 
      dexamethasone given topically for 10 days before the final challenge 
      significantly inhibited the ear swelling and reduced the expression of 
      interferon-gamma mRNA. Dexamethasone inhibited the accumulation of eosinophils 
      completely, although tacrolimus did not. Both drugs did not affect the elevation 
      of serum IgE levels. Tacrolimus significantly inhibited the scratching behavior, 
      whereas dexamethasone failed to affect it. Repeated DNFB challenge depleted 
      substance P in the dermis. Treatment with tacrolimus before the final challenge 
      completely inhibited the recovery of substance P content, whereas dexamethasone 
      facilitated the recovery. DNFB-induced ear swelling and scratching behavior were 
      significantly inhibited by FK888, a tachykinin NK(1) receptor antagonist. 
      Therefore, substance P seems to participate in the induction of ear swelling and 
      scratching behavior upon final challenge with DNFB, and depletion of substance P 
      by tacrolimus in the dermis contributes to its inhibition of ear swelling and 
      scratching behavior at least in part.
FAU - Inagaki, Naoki
AU  - Inagaki N
AD  - Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu 
      Pharmaceutical University, 5-6-1 Mitahorahigashi, Gifu 502-8585, Japan. 
      inagakin@gifu-pu.ac.jp
FAU - Shiraishi, Noriko
AU  - Shiraishi N
FAU - Igeta, Katsuhiro
AU  - Igeta K
FAU - Nagao, Masafumi
AU  - Nagao M
FAU - Kim, John Fan
AU  - Kim JF
FAU - Chikumoto, Takao
AU  - Chikumoto T
FAU - Itoh, Tomokazu
AU  - Itoh T
FAU - Katoh, Hideo
AU  - Katoh H
FAU - Tanaka, Hiroyuki
AU  - Tanaka H
FAU - Nagai, Hiroichi
AU  - Nagai H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091007
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 33507-63-0 (Substance P)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Dermatitis, Atopic/drug therapy/immunology/metabolism/physiopathology
MH  - Dexamethasone/pharmacology
MH  - Ear/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Pruritus/*drug therapy/*metabolism/physiopathology
MH  - Substance P/*deficiency/*metabolism
MH  - Tacrolimus/*pharmacology/*therapeutic use
EDAT- 2009/10/13 06:00
MHDA- 2010/02/18 06:00
CRDT- 2009/10/13 06:00
PHST- 2008/11/10 00:00 [received]
PHST- 2009/09/10 00:00 [revised]
PHST- 2009/09/10 00:00 [accepted]
PHST- 2009/10/13 06:00 [entrez]
PHST- 2009/10/13 06:00 [pubmed]
PHST- 2010/02/18 06:00 [medline]
AID - S0014-2999(09)00827-9 [pii]
AID - 10.1016/j.ejphar.2009.09.043 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2010 Jan 25;626(2-3):283-9. doi: 10.1016/j.ejphar.2009.09.043. 
      Epub 2009 Oct 7.