Participation of histamine H3 receptors in experimental allergic rhinitis of mice.
The present study was performed to study the participation of histamine H(3) receptors in nasal symptoms using Sch 50971, a potent and selective agonist of the H(3) receptor. Repeated topical application of antigen caused an increase in sneezing and nasal rubbing in sensitized mice. Oral administration of Sch 50971 and imetit, specific H(3)-receptor agonists, resulted in an inhibition of nasal symptoms induced by an antigen similar to an H(1)-receptor antagonist, cetirizine. Furthermore, simultaneous use of H(3)-receptor agonists, Sch 50971 or imetit, and an H(1)-receptor antagonist, cetirizine, caused a significant inhibitory effect on nasal symptoms at doses that showed no effect when used separately. The number of eosinophils in the nasal mucosa of mice sensitized with antigen was significantly decreased by cetirizine; however, Sch 50971 and imetit had no effect on eosinophil infiltration. These results clearly indicate that H(3) receptors are involved in the etiology of nasal allergy, and the stimulation of H(3) receptors may be useful as a novel therapeutic approach in nasal allergy.
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Okayama, Japan.
Emiko
E
Yokota
Shoji
S
Kuyama
Yukio
Y
Sugimoto
Masami
M
Ogawa
Chiaki
C
Kamei
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D017332:Cetirizine / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D005260:Female; D017442:Histamine Agonists / Q000494:pharmacology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010047:Ovalbumin; D011537:Pruritus / Q000378:metabolism / Q000517:prevention & control; D011759:Pyrrolidines / Q000494:pharmacology; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000378:metabolism*; D012221:Rhinitis, Allergic, Perennial / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D012912:Sneezing / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
C115122:4-(4-methyl-3-pyrrolidinyl)-1H-imidazole dihydrochloride; D018926:Anti-Allergic Agents; D017442:Histamine Agonists; D039563:Histamine H1 Antagonists, Non-Sedating; D007093:Imidazoles; D011759:Pyrrolidines; D018100:Receptors, Histamine H3; C077430:imetit; D010047:Ovalbumin; D013890:Thiourea; D017332:Cetirizine