Involvement of kinins in hyperresponsiveness induced by platelet activating factor in the human nasal airway.
1. The aim of this study was to investigate the role of kinins in the development of nasal hyperresponsiveness induced by platelet activating factor (PAF) in normal human subjects. 2. Intranasal administration of PAF, 60 micrograms, induced an increased responsiveness to histamine, 200 micrograms per nostril, 6 h later. This effect was abolished by pretreatment with the bradykinin B2 receptor antagonists icatibant and [1-adamantaneacetyl-D-Arg0,Hyp3,beta-(2-thienyl)-Al a5,8,D-Phe7]-bradykinin ([Ad]-BK), both at 200 micrograms, every 2 h following PAF administration. 3. In a separate experiment, utilizing the same protocol, nasal lavage was used to measure the release of mediators into the nasal cavity following treatment with PAF. PAF increased the levels of eosinophil cationic protein (ECP) and kinin detected in the lavage samples, compared with a saline control. The levels of these mediators were reduced by pretreatment with either icatibant or [Ad]-BK. 4. Administration of lyso-PAF, 60 micrograms intranasally, did not cause a rise in kinin or ECP levels in nasal lavage fluid. 5. Exogenous bradykinin, 500 micrograms, or a saline control, applied topically to the nasal mucosa every 30 min for 2 h, failed to cause hyperresponsiveness to histamine. 6. We conclude that bradykinin itself does not cause hyperresponsiveness, but is involved in the hyperresponsiveness induced by PAF in the human nasal airway.
Turner
P J
PJ
Department of Pharmacology, University College London.
Dear
J W
JW
Foreman
J C
JC
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D019540:Area Under Curve; D001798:Blood Proteins / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D047091:Eosinophil Granule Proteins; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007705:Kinins / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D009296:Nasal Cavity / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000633:toxicity*; D043782:Receptor, Bradykinin B2; D012260:Ribonucleases; D007507:Therapeutic Irrigation
D001798:Blood Proteins; D065168:Bradykinin Receptor Antagonists; D047091:Eosinophil Granule Proteins; D007705:Kinins; D010972:Platelet Activating Factor; D043782:Receptor, Bradykinin B2; C074544:bradykinin, 1-adamantanecarboxylic acid-Arg(0)-Hyp(3)-Thi(5,8)-Phe(7)-; C065679:icatibant; D012260:Ribonucleases; D000218:Adamantane; D001920:Bradykinin