Inhibition of guinea pig skin allergic reactions by nonpeptide bradykinin B2 receptor antagonist FR173657.
BACKGROUND
Kinins, which cause vascular permeability enhancement (VPE) through bradykinin (BK) B2 receptors, are released at allergic reaction sites; however, the role kinins play in the lesions is still unknown. To determine whether kinins contribute to allergic reactions, the effect of a potent, nonpeptide BK B2-receptor-specific antagonist, FR173657, on VPE induced in the reaction sites was investigated.


METHODS
Type I allergic reaction was induced by intradermal injections of dinitrophenol (DNP)-bovine serum albumin (BSA) into guinea pigs having received an intravenous injection of anti-DNP antiserum a week before. Type III allergic reaction was induced by intradermal injections of BSA into animals sensitized with subcutaneous injections of complete Freund's adjuvant-emulsified BSA 2 weeks before. VPE and swelling were measured by the leakage of intravenously injected dye and double thickness, respectively, at allergic reaction sites. FR173657 (4 mg/kg body weight) was administered orally 30 min before antigen injection.


RESULTS
In the type I allergy model, FR173657 inhibited 34% of the early-phase VPE, which occurs a few minutes after antigen injection, and 50% of the subsequent swelling at the allergic reaction sites. In the type III allergy model, FR173657 also inhibited 30% of the early VPE but neither the late VPE, which occurs from 1 h to at least 24 h after the antigen injection, nor the following swelling at the allergic reaction sites. FR173657 inhibited BK-induced VPE almost completely without affecting histamine-induced VPE.


CONCLUSIONS
Kinins contribute significantly to the VPE induced in the animal allergy models. FR173657 may be useful for the therapy of human allergic diseases.
Division of Molecular Pathology, Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
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T
Mori
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Imamura
D000818:Animals; D065168:Bradykinin Receptor Antagonists; D004140:Dinitrophenols / Q000276:immunology; D006168:Guinea Pigs; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D011804:Quinolines / Q000276:immunology* / Q000627:therapeutic use*; D043782:Receptor, Bradykinin B2; D012710:Serum Albumin, Bovine / Q000276:immunology; D012867:Skin / Q000276:immunology*
D065168:Bradykinin Receptor Antagonists; D004140:Dinitrophenols; C105311:FR 173657; D011804:Quinolines; D043782:Receptor, Bradykinin B2; D012710:Serum Albumin, Bovine