Peptide and non-peptide bradykinin receptor antagonists: role in allergic airway disease.
Kinins are proinflammatory peptides that mediate a variety of pathophysiological responses. These actions occur through stimulation of two pharmacologically distinct receptor subtypes B1 and B2. In both human and animal airways, the majority of kinin-induced effects including bronchoconstriction, increases in vascular permeability and mucus secretion and cholinergic and sensory nerve stimulation appear to be bradykinin B2-receptor mediated. Peptidic and non-peptidic receptor antagonists have been developed as potential therapeutic agents. These antagonists are effective in blocking kinin-induced effects in a variety of animal models and in some instances, have been used effectively in animal models of allergic airway disease to alleviate allergen-induced pathophysiological airway responses. This review summarizes relevant studies supporting the evidence that bradykinin B2 receptor antagonism and/or upstream inhibition of tissue kallikrein will be beneficial in the treatment of inflammatory airway diseases.
Abraham
William M
WM
Miller School of Medicine, University of Miami at Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, Florida 33140, USA. abraham@msmc.com
Scuri
Mario
M
Farmer
Stephen G
SG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D065094:Bradykinin B2 Receptor Antagonists; D004195:Disease Models, Animal; D006801:Humans; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism; D020840:Tissue Kallikreins / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; C098525:B 9340; D065094:Bradykinin B2 Receptor Antagonists; C105311:FR 173657; D011804:Quinolines; D043782:Receptor, Bradykinin B2; C065679:icatibant; D020840:Tissue Kallikreins; D001920:Bradykinin