arachidonic-acid-omega-9-hydroperoxide and Pruritus

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 (BLT(1) receptor antagonist), but by LY255283 (BLT(2) 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 (H(1)) and several serotonin receptors (5-HT(1), 5-HT(2), and 5-HT(3)). As a result, 12(S)-HPETE-induced scratching was suppressed by capsaicin (TRPV1 receptor agonist), but not by capsazepine (TRPV1 receptor antagonist). Additionally, chlopheniramine (H(1) receptor antagonist) did not suppress 12(S)-HPETE-induced scratching, but cyproheptadine (H(1) receptor and serotonin 5-HT(2) 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-HT(1) receptor antagonist), or ketanserin (5-HT(2) receptor antagonist), but not by ondansetron (5-HT(3) receptor antagonist), after intradermal injection of 12(S)-HPETE. These results suggest that serotonin 5-HT(1/2) 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.

Topics: Animals; Behavior, Animal; Leukotrienes; Male; Mice; Mice, Inbred ICR; Pruritus; Receptors, Histamine H1; Receptors, Serotonin, 5-HT1; Receptors, Serotonin, 5-HT2; Receptors, Serotonin, 5-HT3; TRPV Cation Channels

The itch-associated responses evoked by intradermal injection of 12(S)-HPETE and leukotriene B4 were compared in ICR-mice. 12(S)-HPETE and leukotriene B4 (0.01-0.2 nmol/site) induced scratching of the injected site, respectively; the dose-responses were a peak at 0.05 nmol/site (12(S)-HPETE) or 0.03 nmol/site (leukotriene B4). The scratching response by 12(S)-HPETE (0.05 nmol/site) started within 1 min, peaked in the first 10 min period, had almost subsided by 25 min whereas the effect of leukotriene B4 peaked in the second 10 min. The effect of leukotriene B4 is slightly stronger than that of 12(S)-HPETE in 40 min of count. The scratching induced by 12(S)-HPETE was inhibited by capsaicin, naltrexon, and LY255283. These results suggest the possibility that 12-lipoxygenase product can be added to a new member of an endogenous itch mediator in the skin.

Topics: Animals; Capsaicin; Dose-Response Relationship, Drug; Leukotriene B4; Leukotrienes; Male; Mice; Mice, Inbred ICR; Naltrexone; Pruritus; Receptors, Leukotriene B4