PMID- 23271050
OWN - NLM
STAT- MEDLINE
DCOM- 20130617
LR  - 20220129
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 27
IP  - 4
DP  - 2013 Apr
TI  - Superoxide generation and leukocyte accumulation: key elements in the mediation 
      of leukotriene B(4)-induced itch by transient receptor potential ankyrin 1 and 
      transient receptor potential vanilloid 1.
PG  - 1664-73
LID - 10.1096/fj.12-221218 [doi]
AB  - The underlying mechanisms of itch are poorly understood. We have investigated a 
      model involving the chemoattractant leukotriene B(4) (LTB(4)) that is up-regulated in 
      common skin diseases. Intradermal injection of LTB4 (0.1 nmol/site) into female 
      CD1 mice induced significant scratching movements (used as an itch index) 
      compared with vehicle-injected (0.1% bovine serum albumin-saline) mice. 
      Intraperitoneal transient receptor potential (TRP) channel antagonist treatment 
      significantly inhibited itch as follows: TRP vanilloid 1 (TRPV1) antagonist 
      SB366791 (0.5 mg/kg, by 97%) and the TRP ankyrin 1 (TRPA1) antagonists TCS 
      5861528 (10 mg/kg; 82%) and HC-030031 (100 mg/kg; 76%). Leukotriene B(4) receptor 2 
      antagonism by LY255283 (5 mg/kg i.p.; 62%) reduced itch. Neither TRPV1-knockout 
      (TRPV1-KO) nor TRPA1-knockout (TRPA1-KO mice exhibited LTB(4)-induced itch compared 
      with their wild-type counterparts. The reactive oxygen species scavengers 
      N-acetylcysteine (NAC; 204 mg/kg i.p.; 86%) or superoxide dismutase (SOD; 10 
      mg/kg i.p.; 83%) also inhibited itch. LTB4-induced superoxide release was 
      attenuated by TCS 5861528 (56%) and HC-030031 (66%), NAC (58%), SOD (50%), and 
      LY255283 (59%) but not by the leukotriene B4 receptor 1 antagonist U-75302 (9 
      nmol/site) or SB366791. Itch, superoxide, and myeloperoxidase generation were 
      inhibited by the leukocyte migration inhibitor fucoidan (10 mg/kg i.v.) by 80, 
      61, and 34%, respectively. Myeloperoxidase activity was also reduced by SB366791 
      (35%) and SOD (28%). TRPV1-KO mice showed impaired myeloperoxidase release, 
      whereas TRPA1-KO mice exhibited diminished production of superoxide. This result 
      provides novel evidence that TRPA1 and TRPV1 contribute to itch via distinct 
      mechanisms.
FAU - Fernandes, Elizabeth S
AU  - Fernandes ES
AD  - Programa de Pos-Graduacao em Biologia Parasitaria, Universidade Ceuma, Sao Luis, 
      Brazil.
FAU - Vong, Chi Teng
AU  - Vong CT
FAU - Quek, Samuel
AU  - Quek S
FAU - Cheong, Jessica
AU  - Cheong J
FAU - Awal, Salma
AU  - Awal S
FAU - Gentry, Clive
AU  - Gentry C
FAU - Aubdool, Aisah A
AU  - Aubdool AA
FAU - Liang, Lihuan
AU  - Liang L
FAU - Bodkin, Jennifer V
AU  - Bodkin JV
FAU - Bevan, Stuart
AU  - Bevan S
FAU - Heads, Richard
AU  - Heads R
FAU - Brain, Susan D
AU  - Brain SD
LA  - eng
GR  - 19296/VAC_/Versus Arthritis/United Kingdom
GR  - BB/E527098/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - 19296/ARC_/Arthritis Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121227
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Ankyrins)
RN  - 0 (Receptors, Leukotriene B4)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, human)
RN  - 0 (Transient Receptor Potential Channels)
RN  - 11062-77-4 (Superoxides)
RN  - 1HGW4DR56D (Leukotriene B4)
SB  - IM
MH  - Animals
MH  - Ankyrins/pharmacology
MH  - Female
MH  - Leukocytes/drug effects/*metabolism
MH  - Leukotriene B4/*pharmacology
MH  - Mice
MH  - Mice, Knockout
MH  - Pruritus/drug therapy/metabolism
MH  - Receptors, Leukotriene B4/antagonists & inhibitors
MH  - Superoxides/*metabolism
MH  - TRPV Cation Channels/metabolism
MH  - Transient Receptor Potential Channels/*metabolism
EDAT- 2012/12/29 06:00
MHDA- 2013/06/19 06:00
CRDT- 2012/12/29 06:00
PHST- 2012/12/29 06:00 [entrez]
PHST- 2012/12/29 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
AID - fj.12-221218 [pii]
AID - 10.1096/fj.12-221218 [doi]
PST - ppublish
SO  - FASEB J. 2013 Apr;27(4):1664-73. doi: 10.1096/fj.12-221218. Epub 2012 Dec 27.