Platelet-activating factor (PAF)-induced rhinitis and involvement of PAF in allergic rhinitis in guinea pigs.
The effects of inhaled PAF on the guinea pig nasal mucosa were investigated. Intranasal pressure (INP) was recorded as an index of intranasal resistance. To access the capillary premeability of nasal mucosa, exudation of Evans blue into the nasal lavage fluid was determined. Inhalations of histamine and PAF markedly and significantly increased INP and dye exudation into the nasal cavities. The two responses to PAF were about 20-fold and 70-fold stronger than those of histamine, respectively. A PAF antagonist, CV-3988, significantly antagonized both the PAF-induced increases in INP and dye exudation. Indomethacin and OKY-046 had no effect on the PAF-induced responses. FPL-55712 inhibited the PAF-induced increases in INP and dye exudation by 52% and 40%, respectively. Ovalbumin (OA) antigen challenge by inhalation to sensitized guinea pigs resulted in significant increases in both INP and dye exudation. These two responses to 30 mg/ml OA were inhibited by CV-3988 (10 mg/kg, i.v.) by 55% and 40%, respectively. From the above results, it is indicated that: 1) inhalation of PAF evokes rhinitis-like symptoms through activation of PAF receptors, 2) the PAF-induced rhinitis is, in a part, mediated by leukotrienes, and 3) PAF might be involved in allergic rhinitis.
Misawa
M
M
Department of Applied Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Iwamura
S
S
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002200:Capillary Resistance / Q000187:drug effects*; D005070:Evans Blue; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects; D010972:Platelet Activating Factor / Q000009:adverse effects*; D012220:Rhinitis / Q000139:chemically induced*
D010972:Platelet Activating Factor; D005070:Evans Blue; D006632:Histamine