Nasal allergic response mediated by histamine H3 receptors in murine allergic rhinitis.
BACKGROUND
Histamine is one of the most important chemical mediators causing nasal allergic symptoms, and H1 receptor antagonist have been used as the treatment first choice in nasal allergy. The presence of H3 receptors has also been determined in the human nasal mucosa, but few studies have investigated the involvement of H3 receptors in nasal allergy.


OBJECTIVE
We used a murine allergic model to investigate the presence of nasal mucosa H3 receptor mRNA and any H3 receptor agonist or antagonist influences on clinical nasal allergic symptoms.


METHODS
H3 receptor mRNA in nasal mucosa was investigated by reverse-transcription polymerase chain reaction. OVA-sensitized mice were given an intraperitoneal injection of H3 receptor agonist or antagonist, and clinical nasal allergic symptoms were scored over 10 minutes after nasal provocation of OVA. Inhibition of nasal allergic symptoms was also examined using an H1 receptor antagonist alone and using a both an H3 receptor agonist and an H1 receptor antagonist.


RESULTS
H3 receptor mRNA was identified in the murine nasal mucosa. The H3 receptor agonist (R)-alpha-metylhistamine significantly inhibited clinical nasal allergic symptoms of OVA-sensitized mice. The H3 receptor agonist and H1 receptor antagonist inhibited clinical nasal allergic symptoms in the murine allergic model more strongly than the single drug.


CONCLUSIONS
The foregoing results indicate that H3 receptors are involved in modulation of nasal allergy. H3 receptor agonists can also be useful as a novel therapeutic approach in nasal allergy. Both H3 receptor agonist and H1 receptor antagonist may be more effective than a single drug.
Nakaya
Muneo
M
Department of Otolaryngology, Faculty of Medicine, University of Tokyo, Japan. muneo@interlink.or.jp
Fukushima
Yasushi
Y
Takeuchi
Naonobu
N
Kaga
Kimitaka
K
D000485:Allergens / Q000009:adverse effects; D000818:Animals; D017442:Histamine Agonists / Q000276:immunology / Q000494:pharmacology; D006633:Histamine Antagonists / Q000276:immunology / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology*; D010047:Ovalbumin / Q000009:adverse effects; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000276:immunology*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*
D000485:Allergens; D017442:Histamine Agonists; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D018100:Receptors, Histamine H3; D010047:Ovalbumin