Effect of histamine H4 receptor antagonist on allergic rhinitis in mice.
The aim of this study was to clarify the effect of histamine H(4) receptor antagonist, JNJ7777120 (1-[(5-Chloro-1H-indol-2-yl)carbonyl]-4-methyl-piperazine) on allergic rhinitis in mice. We measured allergic symptoms (sneezing and nasal rubbing), serum total IgE and the levels of cytokines in nasal lavage fluid. Histamine H(4) receptor antagonist, JNJ7777120, caused the dose-dependent inhibition of nasal symptoms by single and repeated intranasal administrations; however, JNJ7777120 caused no inhibition of serum total IgE by single and repeated intranasal administrations. Therefore, we investigated the effect of JNJ7777120 by oral administration. JNJ7777120 also caused a significant inhibition of nasal symptoms by both single and repeated oral administrations. In addition, repeated oral administration of JNJ7777120 caused significant inhibition of serum total IgE. Furthermore, JNJ7777120 caused a significant decrease in the levels of IL-4 and a significant increase in the levels of IFN-gamma in nasal lavage fluid. These results indicated that histamine H(4) receptor is closely related with allergic rhinitis and is important in the pathogenesis of allergic rhinitis. From these results, it can be concluded that histamine H(4) receptor antagonist might be a new strategy to treat allergic rhinitis with immunomodulatory function.
Takahashi
Yuji
Y
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Okayama 700-8530, Japan.
Kagawa
Yoto
Y
Izawa
Kana
K
Ono
Rie
R
Akagi
Masaaki
M
Kamei
Chiaki
C
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D007665:Ketotifen / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D017817:Nasal Lavage Fluid / Q000276:immunology; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000276:immunology
D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; C498829:Hrh4 protein, mouse; D007211:Indoles; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D015847:Interleukin-4; D007073:Immunoglobulin E; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D007371:Interferon-gamma; D007665:Ketotifen