title: Hyperresponsiveness to tussive stimuli in cigarette smoke-exposed guinea-pigs: a role for capsaicin-sensitive, calcitonin gene-related peptide-containing nerves.
abstract: Environmental pollutants may induce airway hyperresponsiveness to bronchonconstrictor stimuli, but if there is a concomitant change in other defensive reflexes, like the cough reflex, is not known. We have examined how two weeks' exposure to cigarette smoke influences airway sensitivity to inhaled irritants acting mainly through capsaicin-sensitive sensory neurons (citric acid, capsaicin) or rapidly adapting stretch receptors (cigarette smoke, histamine). Guinea-pigs were exposed, over a period of one hour, to cigarette smoke or room air, twice daily for 2 weeks. Twenty-four hours after the end of the smoke exposure coughing produced by nebulized citric acid (0.40 M) and capsaicin (30 microM) was enhanced 3.7 (P less than 0.001) and 2.5 (P less than 0.05) times, respectively, whereas the cigarette smoke-induced cough was unchanged. The enhanced responsiveness gradually returned to normal over a period of three weeks and was not mediated by cyclo-oxygenase products since it was not affected by indomethacin (3 mumols kg-1). In contrast, the broncho-constrictor responses to citric acid, capsaicin, cigarette smoke and histamine (0.70 mM) were not altered by inhalation of cigarette smoke. Smoke-exposed animals had a significantly (P less than 0.05) increased amount of calcitonin gene-related peptide-like material (CGRP, contained in capsaicin-sensitive sensory neurons) in tracheal tissue, suggesting that chronic irritation stimulates peptide synthesis. The amount of neuropeptide Y-like material (in autonomic motor nerves) in pulmonary tissue was not changed indicating some 'specificity' in the irritative effect of smoke. It is concluded that prolonged exposure to cigarette smoke produces a tussive hyperresponsiveness that seems to involve specifically capsaicin-sensitive, CGRP-containing sensory neurons mediating cough. The present data demonstrate the development of a 'sensory' hyperresponsiveness, separate from airway hyperresponsiveness to bronchoconstrictor agents.
authors.affiliation: Department of Pharmacology, AB Draco, Lund, Sweden.
authors.forename: J A
authors.initials: JA
authors.lastname: Karlsson
authors.forename: C
authors.initials: C
authors.lastname: Zackrisson
authors.forename: J M
authors.initials: JM
authors.lastname: Lundberg
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D003371:Cough / Q000503:physiopathology*; D005260:Female; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000276:immunology / Q000378:metabolism; D011863:Radioimmunoassay; D012018:Reflex / Q000187:drug effects; D012907:Smoking / Q000503:physiopathology*; D012912:Sneezing / Q000187:drug effects
chemical_list: D009478:Neuropeptide Y; D009479:Neuropeptides; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D007213:Indomethacin