Involvement of the BLT 2 receptor in the itch-associated scratching induced by 12-(S)-lipoxygenase products in ICR mice

H. J. Kim, D. K. Kim, H. Kim, J. Y. Koh, K. M. Kim, M. S. Noh, S. Lee, S. Kim, S. H. Park, J. J. Kim, S. Y. Kim, C. H. Lee

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Background and purpose: Recently, we reported that 12(S)-HPETE (12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid) induces scratching in ICR mice. We hypothesized that 12(S)-HPETE might act as an agonist of the low-affinity leukotriene B 4 receptor BLT 2. To confirm the involvement of the BLT 2 receptor in 12(S)-HPETE-induced scratching, we studied the scratch response using the BLT 2 receptor agonists compound A (4′-{[pentanoyl (phenyl) amino]methyl}-1,1′-biphenyl-2- carboxylic acid) and 12(S)-HETE (12(S)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid). Experimental approach: A video recording was used to determine whether the BLT 2 receptor agonists caused itch-associated scratching in ICR mice. Selective antagonists and several chemicals were used. Key results: Both 12(S)-HETE and compound A dose dependently induced scratching in the ICR mice. The dose-response curve for compound A showed peaks at around 0.005-0.015 nmol per site. Compound A- and 12(S)-HETE-induced scratching was suppressed by capsaicin and naltrexon. We examined the suppressive effects of U75302 (6-[6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl]-1,5-hexanediol, the BLT 1 receptor antagonist) and LY255283 (1-[5-ethyl-2-hydroxy-4-[[6- methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]-ethanone, the BLT 2 receptor antagonist) on the BLT 2 agonist-induced scratching. LY255283 suppressed compound A- and 12(S)-HETE-induced scratching, but U75302 did not. LY255283 required a higher dose to suppress the compound A-induced scratching than it did to suppress the 12(S)-HETE-induced scratching. One of the BLT 2 receptor agonists, 12(R)-HETE (12(R)-hydroxyeicosa-5Z,8Z,10E,14Z- tetraenoic acid), also induced scratching in the ICR mice. Conclusions and implications: Our present results corroborate the hypothesis that the BLT 2 receptor is involved in 12(S)-lipoxygenase-product-induced scratching in ICR mice. We also confirmed that this animal model could be a valuable means of evaluating the effects of BLT 2 receptor antagonists.

Original languageEnglish
Pages (from-to)1073-1078
Number of pages6
JournalBritish Journal of Pharmacology
Volume154
Issue number5
DOIs
StatePublished - Jul 2008

Keywords

  • 12(R)-HETE
  • 12(S,R)-HETE
  • BLT receptor
  • Compound A
  • LY255283
  • Scratching

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