Role of tachykinins in the bronchoconstriction induced by HCl intraesophageal instillation in the rabbit.
Gastroesophageal acid reflux (GER) is a common disorder associated with the exacerbation of asthma. In this study we investigated the effects on the airways of intraoesophageal HCl instillation in the rabbit and the role of tachykinins in these effects. In anaesthetized New Zealand rabbits bronchopulmonary functions [total lung resistance (R(L)) and dynamic compliance (C(dyn))] were calculated before and after HCl intraoesophageal instillation. Infusion of HCl induced a significant bronchoconstriction (P < 0.05) in the terms of R(L) and C(dyn) changes, that were increased by phosphoramidon pre-treatment and reduced by capsaicin pre-treatment. Moreover, a pre-treatment with SR 48968, a tachykinin NK2 receptor antagonist, or SR 140333, a NK1 receptor antagonist, significantly inhibited the bronchoconstriction induced by intraoesophageal HCl infusion in terms of R(L) and C(dyn)changes. Finally, the HCl induced bronchoconstriction was unaffected by SR 142801, a tachykinin NK3 receptor antagonist. In conclusion these results suggest that bronchoconstriction induced by intraoesophageal HCl infusion is mainly dependent on the release of tachykinins and that both NK1 and NK2 tachykinin receptors are involved.
Gallelli
L
L
Department of Experimental Medicine, Section of Pharmacology Leonardo Donatelli, Faculty of Medicine and Surgery, 2nd University of Naples, Via Costantinopoli 16-80138, Naples, Italy.
D'Agostino
B
B
Marrocco
G
G
De Rosa
G
G
Filippelli
W
W
Rossi
F
F
Advenier
C
C
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D004947:Esophagus / Q000502:physiology*; D006020:Glycopeptides / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000008:administration & dosage; D007441:Intubation, Gastrointestinal; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D011480:Protease Inhibitors / Q000494:pharmacology; D011817:Rabbits; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D012129:Respiratory Function Tests; D013268:Stimulation, Chemical; D015320:Tachykinins / Q000502:physiology*
D006020:Glycopeptides; D064729:Neurokinin-1 Receptor Antagonists; D011480:Protease Inhibitors; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; D006851:Hydrochloric Acid; D002211:Capsaicin; C008890:phosphoramidon