A bradykinin antagonist inhibits both bradykinin- and the allergen-induced airway response in primates.
Bradykinin is a mediator of bronchoconstriction and may play a role in the development of the asthmatic response after antigen challenge. Our objective was to study the effectiveness of NPC 17731 as a specific bradykinin beta 2-receptor antagonist and as an antagonist of the allergen-induced early phase of asthma. A primate model was used for all studies. Intracutaneous end-point titrations were performed with bradykinin. A shift of the bradykinin end-point titer was seen when NPC 17731 was injected by the intradermal route prior to performing the end-point titration. Using an aerosolized bradykinin or Ascaris suum antigen airway threshold challenge system, inhibition of the bradykinin or Ascaris airway response was evaluated after pretreatment with aerosolized NPC 17731. NPC 17731 proved to be a safe, effective specific bradykinin receptor antagonist in both cutaneous and airway challenges. NPC 17731 was able to inhibit the antigen-induced airway response in the primate. Bradykinin may play a larger role in mediating the early phase of the antigen-induced asthmatic response than previously was appreciated.
Hogan
M B
MB
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
Harris
K E
KE
Protter
A A
AA
Patterson
R
R
D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000276:immunology; D017165:Ascaris suum / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D001920:Bradykinin / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D008253:Macaca mulatta; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage*
D000947:Antigens, Helminth; D009842:Oligopeptides; C071327:NPC 17731; D001920:Bradykinin