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 language | English |
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Pages (from-to) | 1073-1078 |
Number of pages | 6 |
Journal | British Journal of Pharmacology |
Volume | 154 |
Issue number | 5 |
DOIs | |
State | Published - Jul 2008 |
Keywords
- 12(R)-HETE
- 12(S,R)-HETE
- BLT receptor
- Compound A
- LY255283
- Scratching