Role of substance P and tachykinin receptor antagonists in citric acid-induced cough in pigs.
The purpose of this work was to investigate the role of tachykinins in cough induced by citric acid (0.8 M) in pigs. With this object, we have studied the effect of citric acid on substance P content in the tracheo-bronchial tree and the effects of substance P and of tachykinin receptor antagonists on citric acid-induced cough. Citric acid exposure significantly increased substance P concentration in both broncho-alveolar and tracheal lavage fluids, while it decreased significantly the substance P content in tracheal mucosa. Substance P did not elicit cough, but significantly potentiated the citric acid-induced cough frequency. Tachykinin NK(1), NK(2) or NK(3) receptor antagonists, SR 140333 (nolpitantium), SR 48968 (saredutant) and SR 142801 (osanetant), respectively, significantly inhibited citric acid-induced cough. The same inhibitory effect of tachykinin receptor antagonists was observed, when substance P was nebulised before citric acid challenge. We conclude that citric acid induces in pigs a release of substance P in the tracheo-bronchial tree, which plays a sensitising role on the cough reflex. The involvement of tachykinin NK(1), NK(2), NK(3) receptors are also demonstrated in this reflex.
Moreaux
B
B
Faculty of Veterinary Medicine, Department of Pharmacology, Pharmacotherapy and Toxicology, University of Liège, Bd de Colonster B 41, B-4000, Liège, Belgium.
Nemmar
A
A
Vincke
G
G
Halloy
D
D
Beerens
D
D
Advenier
C
C
Gustin
P
P
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D019343:Citric Acid / Q000008:administration & dosage*; D003371:Cough / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013556:Swine, Miniature
D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; C085215:SR 140333; D019343:Citric Acid; D013373:Substance P; C073839:SR 48968; C091554:SR 142801