Effects of tachykinin receptor antagonists, FK224 and FK888, in a guinea-pig model of nasal allergy.
The effects of two tachykinin receptor antagonists, FK888 (selective antagonist at the tachykinin NK-1 receptor) and FK224 (dual antagonist at NK-1 and NK-2 tachykinin receptors), on the frequency of sneezing, decrease of nasal patency, and increase of vascular dye leakage induced by antigen challenge upon the guinea-pig nasal mucosa were studied. The animals were sensitized with ovalbumin intraperitoneally. FK224 inhibited and FK888 tended to inhibit the decrease of nasal patency induced by antigen challenge. The increase of vascular dye leakage from nasal mucosa induced by antigen challenge tended to be inhibited by both FK224 and FK888. But both of them did not inhibit the increase of sneezing induced by antigen challenge. We conclude that in the guinea-pig model of nasal allergy, tachykinin receptors mediate plasma leakage and swelling of nasal mucosa induced by antigen challenge, but the participation of an axonal reflex via tachykinin receptors is rather small compared to the direct vascular effect of chemical mediators.
Katahashi
T
T
Department of Otolaryngology, School of Medicine, Chiba University, Japan.
Konno
A
A
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000941:Antigens / Q000276:immunology; D002199:Capillary Permeability / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology*; D064729:Neurokinin-1 Receptor Antagonists; D010047:Ovalbumin / Q000276:immunology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D012912:Sneezing / Q000187:drug effects; D018709:Statistics, Nonparametric
D000941:Antigens; D004151:Dipeptides; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D010456:Peptides, Cyclic; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C075570:FK 224; C078949:FK 888; D010047:Ovalbumin