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 coug h 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 flui ds, while it decreased significantly the substance P content in tracheal mu cosa. Substance P did not elicit cough, but significantly potentiated the c itric acid-induced cough frequency. Tachykinin NK1, NK2 or NK3 receptor ant agonists, SR 140333 (nolpitantium), SR 48968 (saredutant) and SR 142801 (os anetant), 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 t hat citric acid induces in pigs a release of substance P in the tracheo-bro nchial tree, which plays a sensitising role on the cough reflex. The involv ement of tachykinin NK1, NK2, NK3 receptors are also demonstrated in this r eflex. (C) 2000 Elsevier Science B.V. All rights reserved.