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.