Role of histamine H(4) receptor in allergic conjunctivitis in mice.
We investigated the character of histamine H(1) receptor and H(4) receptor in allergic conjunctivitis. Histamine is the most important mediator in allergic conjunctivitis. We measured eye scratching behavior and allergic-like symptoms score, that is, hyperemia and edema in ICR mice, and examined which receptors intimately involved in allergic conjunctivitis. Histamine caused a dose-dependent eye scratching behavior and allergic-like symptoms. Histamine H(1) receptor antagonist (levocabastine) and H(4) receptor antagonist (JNJ7777120) inhibited eye scratching behavior and histamine H(1) receptor antagonist inhibited allergic-like symptoms induced by histamine. Additionally, combination of levocabastine and JNJ7777120 caused more potent inhibition in allergic conjunctivitis. On the other hand, both selective histamine H(1) receptor agonist (HTMT) and selective H(4) receptor agonist (4-methylhistamine) induced a dose-dependent eye scratching behavior and allergic-like symptoms. JNJ7777120 inhibited the effect of HTMT. However, levocabastine caused no inhibition on the response of 4-methylhistamine. H(4) receptor was closely related with allergic conjunctivitis. H(4) receptor antagonists may be effective in allergic conjunctivitis which showed no inhibition by histamine H(1) receptor antagonists.
Nakano
Yoshiyuki
Y
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Takahashi
Yuji
Y
Ono
Rie
R
Kurata
Yasunori
Y
Kagawa
Yoto
Y
Kamei
Chiaki
C
D000818:Animals; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000276:immunology; D006632:Histamine / Q000494:pharmacology / Q000633:toxicity; D017442:Histamine Agonists / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D011537:Pruritus / Q000139:chemically induced* / Q000503:physiopathology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011968:Receptors, Histamine / Q000502:physiology*; D000074040:Receptors, Histamine H4; D016896:Treatment Outcome
D017442:Histamine Agonists; C498829:Hrh4 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D006632:Histamine