Involvement of serotonin receptors 5-HT1 and 5-HT2 in 12(S)-HPETE-induced scratching in mice

The mechanisms of 12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid (12(S)-HPETE)-induced scratching were studied in ICR mice. In a recent paper, we demonstrated that the 12(S)-HPETE-induced scratching was reduced not by U75302 (BLT1 receptor antagonist), but by LY255283 (BLT2 receptor antagonist). In the present study, we tested various compounds to elucidate the mechanism of 12(S)-HPETE-induced scratching relating to transient receptor potential vanilloid type-1 (TRPV1), histamine receptor (H1) and several serotonin receptors (5-HT1, 5-HT2, and 5-HT3). As a result, 12(S)-HPETE-induced scratching was suppressed by capsaicin (TRPV1 receptor agonist), but not by capsazepine (TRPV1 receptor antagonist). Additionally, chlopheniramine (H1 receptor antagonist) did not suppress 12(S)-HPETE-induced scratching, but cyproheptadine (H1 receptor and serotonin 5-HT2 receptor antagonist) potently suppressed the same response. Therefore, we tested several serotonin receptor antagonists to explain the detailed mechanisms relating to serotonin receptors. The scratching was reduced by WAY100635 (5-HT1 receptor antagonist), or ketanserin (5-HT2 receptor antagonist), but not by ondansetron (5-HT3 receptor antagonist), after intradermal injection of 12(S)-HPETE. These results suggest that serotonin 5-HT1/2 receptors are implicated in 12(S)-HPETE-induced scratching in ICR mice and that the TRPV1 receptor might not be directly related to 12(S)-HPETE-induced scratching.