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Kim HJ, Kim DK, Kim H, Koh JY, Kim KM, Noh MS, Lee S, Kim S, Park SH, Kim JJ, Kim SY, Lee CH: Involvement of the BLT2 receptor in the itch-associated scratching induced by 12-(S)-lipoxygenase products in ICR mice. Br J Pharmacol. 2008 Jul;154(5):1073-8. Epub 2008 Jun 9.
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 B4 receptor BLT2. To confirm the involvement of the BLT2 receptor in 12 (S)-HPETE-induced scratching, we studied the scratch response using the BLT2 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 BLT2 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 BLT1 receptor antagonist) and LY255283 (1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl) heptyl] oxy] phenyl]- ethanone, the BLT2 receptor antagonist) on the BLT2 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 BLT2 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 BLT2 receptor antagonists. |
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