Role of substance P in allergic nasal symptoms in rats.
The present study was undertaken to investigate the pathological role of substance P in allergic nasal symptoms in rats. The topical application of substance P caused an increase in the incidence of sneezing and nasal rubbing in a dose-dependent fashion, and at a dose of 30 nM/site it showed a significant effect. L-732,138, a tachykinin NK(1) receptor antagonist, at doses of 3 and 10 mg/kg showed a significant inhibition of the nasal signs induced by exogenous substance P in rats. In addition, L-732,138 also showed a significant inhibition of nasal behavior induced by antigen in actively sensitized rats at the same dose. On the other hand, histamine H(1) receptor antagonists, such as cyproheptadine, epinastine and olopatadine had no effect on the nasal behaviors induced by exogenous substance P, even at higher doses, indicating that exogenous substance P does not cause the degranulation of mucosal mast cells in the rat. Moreover, all the histamine H(1) receptor antagonists showed the dose-dependent inhibition of the nasal signs induced by antigen in actively sensitized rats, which revealed that the inhibition of these drugs was exhibited through the antagonistic effect on histamine H(1) receptors. Therefore, from these results, it is reasonable to conclude that substance P released from the nasal mucosa through the activation of tachykinin NK(1) receptors during the antigen antibody reaction plays an important role in allergic nasal symptoms.
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka 1-1-1, Okayama 700-8530, Japan.
Md Ashequr
MA
Rahman
Toshio
T
Inoue
Chiaki
C
Kamei
D000818:Animals; D000941:Antigens / Q000276:immunology; D003533:Cyproheptadine / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology; D003990:Dibenzoxepins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D000069605:Olopatadine Hydrochloride; D051381:Rats; D017208:Rats, Wistar; D012912:Sneezing / Q000187:drug effects*; D013373:Substance P / Q000633:toxicity*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
D000941:Antigens; D003984:Dibenzazepines; D003990:Dibenzoxepins; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D064729:Neurokinin-1 Receptor Antagonists; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D000069605:Olopatadine Hydrochloride; D003533:Cyproheptadine; D013373:Substance P; D014364:Tryptophan; C053090:epinastine