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 (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.
Dermatologic Drug Research, AmorePacific Corporation R&D Center, Youngin-shi, Kyunggi-do, 449-729, Republic of Korea.
Dae-Kwon
DK
Kim
Hyoung-June
HJ
Kim
Hyuk
H
Kim
Jae-Young
JY
Koh
Kwang-Mi
KM
Kim
Min-Soo
MS
Noh
Jung-Ju
JJ
Kim
Chang-Hoon
CH
Lee
D000818:Animals; D001522:Behavior, Animal; D015289:Leukotrienes / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011537:Pruritus / Q000139:chemically induced*; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000187:drug effects* / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects* / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism
D015289:Leukotrienes; D011969:Receptors, Histamine H1; D044263:Receptors, Serotonin, 5-HT1; D044348:Receptors, Serotonin, 5-HT2; D044406:Receptors, Serotonin, 5-HT3; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C021201:12-HPETE