Substance P is involved in the effect of histamine H3 receptor agonist, Sch 50971 on nasal allergic symptoms in mice.
The aim of this study was to clarify the mechanisms of the inhibitory effect of a histamine H3 receptor agonist, Sch 50971, on nasal signs in an allergic rhinitis model in mice. The severity of allergic rhinitis was assessed by determining the extent of two markers of allergic symptoms (sneezing and nasal rubbing). The topical application of a histamine H3 receptor antagonist, clobenpropit, into the nasal cavities resulted in a dose-dependent increase in sneezing and nasal rubbing, and both Sch 50971 and a tachykinin NK1 receptor antagonist, L-733,060, inhibited these reactions in non-sensitized mice. Sch 50971 caused no inhibition of histamine- and substance P-induced nasal symptoms; however, the reactions induced by capsaicin were significantly decreased by Sch 50971 in non-sensitized mice. Sch 50971 and cetirizine inhibited antigen-induced sneezing and nasal rubbing in sensitized mice. On the other hand, cetirizine inhibited nasal symptoms induced by antigen in capsaicin-pretreated mice, whereas no effect was observed in Sch 50971. From these results, we concluded that Sch 50971 blocked nasal symptoms by the inhibition of substance P release via histamine H3 receptors located on peri]pheral sensory nerve endings.
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Okayama 700-8530, Japan.
Emiko
E
Yokota
Shoji
S
Kuyama
Masami
M
Ogawa
Chiaki
C
Kamei
D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage; D017332:Cetirizine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006632:Histamine / Q000008:administration & dosage; D017442:Histamine Agonists / Q000627:therapeutic use*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000627:therapeutic use; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010880:Piperidines / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use*; D018100:Receptors, Histamine H3 / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D013373:Substance P / Q000008:administration & dosage / Q000378:metabolism*; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives
C115122:4-(4-methyl-3-pyrrolidinyl)-1H-imidazole dihydrochloride; D017442:Histamine Agonists; D039563:Histamine H1 Antagonists, Non-Sedating; D007093:Imidazoles; D010880:Piperidines; D011759:Pyrrolidines; D018100:Receptors, Histamine H3; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D013373:Substance P; D006632:Histamine; D010047:Ovalbumin; D013890:Thiourea; C086108:clobenpropit; D002211:Capsaicin; D017332:Cetirizine