title: Passive smoke effects on cough and airways in young guinea pigs: role of brainstem substance P.
abstract: Children raised with extended exposure to environmental tobacco smoke (ETS) experience increased cough and wheeze. This study was designed to determine whether extended ETS exposure enhances citric acid-induced cough and bronchoconstriction in young guinea pigs via a neurokinin-1 (NK-1) receptor mechanism at the first central synapse of lung afferent neurons, the nucleus tractus solitarius. Guinea pigs were exposed to ETS from 1 to 6 weeks of age. At 5 weeks of age, guide cannulae were implanted bilaterally in the medial nucleus tractus solitarius at a site that produced apnea in response to the glutamate agonist D,L-homocysteic acid. At 6 weeks of age, either vehicle or a NK-1 receptor antagonist, SR 140333, was injected into the nucleus tractus solitarius of the conscious guinea pigs who were then exposed to citric acid aerosol. ETS exposure significantly enhanced citric acid-induced cough by 56% and maximal Penh (a measure of airway obstruction) by 43%, effects that were attenuated by the NK-1 receptor antagonist in the nucleus tractus solitarius. We conclude that in young guinea pigs extended exposure to ETS increases citric acid-induced cough and bronchoconstriction in part by an NK-1 receptor mechanism in the nucleus tractus solitarius.
authors.affiliation: Department of Pediatrics, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA. jpjoad@ucdavis.edu
authors.forename: Jesse P
authors.initials: JP
authors.lastname: Joad
authors.forename: Paul A
authors.initials: PA
authors.lastname: Munch
authors.forename: John M
authors.initials: JM
authors.lastname: Bric
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Evans
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.forename: Chao-Yin
authors.initials: CY
authors.lastname: Chen
authors.forename: Ann C
authors.initials: AC
authors.lastname: Bonham
mesh_terms: D000336:Aerosols; D000367:Age Factors; D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D016084:Bronchoconstriction / Q000502:physiology*; D019343:Citric Acid; D003371:Cough / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*; D006168:Guinea Pigs; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007267:Injections; D008168:Lung / Q000294:innervation; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D017552:Solitary Nucleus / Q000502:physiology; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D000336:Aerosols; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D014028:Tobacco Smoke Pollution; D006710:Homocysteine; C007956:homocysteic acid; C085215:SR 140333; D019343:Citric Acid; D013373:Substance P