Mediator involvement in antigen‐induced bronchospasm and microvascular leakage in the airways of ovalbumin sensitized Brown Norway rats

To determine which mediators are involved in antigen‐induced bronchospasm and microvascular leakage in the airways of ovalbumin sensitised Brown Norway rats we investigated the effect of a histamine H 1 receptor antagonist, mepyramine, a 5‐HT receptor antagonist, methysergide, and a cys‐leukotriene‐1 receptor antagonist, montelukast. Ovalbumin at 1 mg kg −1 i.v. caused a significant increase in microvascular leakage in the airways and at 3 mg kg −1 i.v. caused a significant increase in airways resistance. Histamine (1 mg kg −1 i.v.), 5‐HT (0.1 mg kg −1 i.v.) and leukotriene D 4 (LTD 4 , 50 μg kg −1  i.v.) caused a significant increase in microvascular leakage in the airways. Mepyramine (1 mg kg −1 i.v.), methysergide (0.1 mg kg −1 i.v.), or montelukast (30 mg kg −1 i.v.) inhibited histamine, 5‐HT or LTD 4 ‐induced microvascular leakage respectively. Methysergide (0.1 mg kg −1 i.v.) reduced ovalbumin‐induced microvascular leakage in the trachea and at 0.3 mg kg −1 i.v. inhibited bronchospasm (38 and 58%, respectively). Montelukast (30 mg kg −1 p.o.) reduced ovalbumin‐induced microvascular leakage in airway tissue to basal levels (78%) and inhibited ovalbumin‐induced bronchospasm (50%). Mepyramine (3 mg kg −1 i.v.) had no effect on ovalbumin‐induced leakage or bronchospasm. A combination of all three compounds (mepyramine, methysergide and montelukast) reduced ovalbumin‐induced microvascular leakage in airway tissue to basal levels (70 – 78%) and almost completely inhibited bronchospasm (92%). Antigen‐induced bronchospasm appears to equally involve the activation of 5‐HT and cys‐leukotriene‐1 receptors whereas ovalbumin‐induced microvascular leakage appears to be predominantly mediated by cys‐leukotriene‐1 receptors.British Journal of Pharmacology (2001) 132 , 481–488; doi: 10.1038/sj.bjp.0703847