Effect of antagonists for NK(2)and B(2) receptors on antigen-induced airway responses in allergic rabbits.
The effects of the tachykinin NK(2)receptor antagonist, MEN 11420 (300 nmol/kg) and the bradykinin B(2)receptor antagonist, CP 0597 (17.2 and 172 nmol/kg) were studied in a rabbit model of antigen-induced airway responses. Antigen inhalation induced acute bronchoconstriction, airway hyperresponsiveness to histamine, and pulmonary eosinophil infiltration in 3-month-old rabbits immunized with Alternaria tenuis antigen within 24 h of birth. Treatment with MEN 11420 significantly reduced the acute bronchoconstriction induced by antigen, in terms of lung resistance. Antigen-induced changes in dynamic compliance were unaffected. CP 0597 had no effect on antigen-induced changes in lung function. Neither MEN 11420 nor CP 0597 had a significant effect on the antigen-induced increase in airway responsiveness to inhaled histamine or the pulmonary eosinophil infiltration 24 h after antigen challenge. We conclude that blockade of the NK(2)receptor can alter acute airway responses to antigen, but not antigen-induced eosinophilia or hyperresponsiveness to histamine. We also conclude that bradykinin B(2)receptor-mediated responses do not play a role in airway responses to antigen.
Woisin
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FE
Sackler Institute of Pulmonary Pharmacology, Division of Pharmacology and Therapeutics, GKT School of Biomedical Sciences, Guy's Campus, London, SE1 9RT, UK. frances.woisin@kcl.ac.uk
Matsumoto
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Douglas
G J
GJ
Paul
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Whalley
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D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000517:prevention & control*; D065168:Bradykinin Receptor Antagonists; D016535:Bronchial Hyperreactivity / Q000503:physiopathology / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D018893:Bronchoalveolar Lavage; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007428:Intradermal Tests; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*
D065168:Bradykinin Receptor Antagonists; D001993:Bronchodilator Agents; C107323:CP 0597; C107754:MEN 11420; D009842:Oligopeptides; D010456:Peptides, Cyclic; D018039:Receptors, Tachykinin