Mechanism of irritant-induced cough: studies with a kinin antagonist and a kallikrein inhibitor.
It has been suggested that bradykinin may play a role in stimulating cough in at least one pathological condition in humans. We have employed an animal model to investigate the possible role of this peptide in irritant-induced cough. The kinin antagonist Hoe 140 and codeine both produced dose-related inhibition of cough responses to inhalation of citric acid or bradykinin aerosols by conscious guinea pigs. The selective tissue kallikrein inhibitor CH694 inhibited cough caused by citric acid but not by bradykinin. Indomethacin pretreatment attenuated the responses to both stimuli as did phosphoramidon. It is concluded that cough produced by citric acid inhalation may be mediated, at least in part, by generation of kinins; secondary to this, a release of prostanoids also appears to participate in the response.
Featherstone
R L
RL
Immunopharmacology Group, Southampton General Hospital, United Kingdom.
Parry
J E
JE
Evans
D M
DM
Jones
D M
DM
Olsson
H
H
Szelke
M
M
Church
M K
MK
D000280:Administration, Inhalation; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D019343:Citric Acid / Q000008:administration & dosage; D003061:Codeine / Q000494:pharmacology / Q000627:therapeutic use; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007509:Irritants / Q000008:administration & dosage; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D007705:Kinins / Q000037:antagonists & inhibitors*; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology
D065168:Bradykinin Receptor Antagonists; C104372:CH 694; D004151:Dipeptides; D006020:Glycopeptides; D007509:Irritants; D007705:Kinins; D011480:Protease Inhibitors; D019343:Citric Acid; C065679:icatibant; D007610:Kallikreins; D001920:Bradykinin; C008890:phosphoramidon; D003061:Codeine; D007213:Indomethacin