title: Chronic smoking enhances tachykinin synthesis and airway responsiveness in guinea pigs.
abstract: This study tests the hypothesis that the bronchial hyperreactivity induced by chronic cigarette smoke (CS) exposure involves the increased expression and release of tachykinins and calcitonin gene-related peptide (CGRP) from afferent nerve fibers innervating the airways. In guinea pigs chronically exposed to CS (20 min twice daily for 14-17 d), peak response in total lung resistance to capsaicin (1.68 microg/kg, intravenously) was significantly greater than that evoked by the same dose of capsaicin in control (air-exposed) animals. This augmented response in CS-exposed animals was abolished after treatment with CP-99994 and SR-48968, the neurokinin (NK)-1 and NK-2 receptor antagonists, suggesting the involvement of tachykinins in chronic CS-induced airway hyperresponsiveness (AHR). Further, substance P (SP)-like immunoreactivity (LI) and CGRP-LI in the airway tissue were significantly greater in the CS animals than in the control animals. Finally, beta-preprotachykinin (PPT, a splice variant from the PPT A gene encoding tachykinins including SP and NKA) messenger RNA levels as measured by in situ hybridization histochemistry displayed a significant increase in jugular ganglion neurons but not in dorsal root or nodose ganglion neurons. These data suggest that chronic CS-induced AHR is related to an increase in SP synthesis and release in jugular ganglion neurons innervating the lungs and airways.
authors.affiliation: Department of Physiology, University of Kentucky, Lexington, Kentucky 40536, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kwong
authors.forename: Z X
authors.initials: ZX
authors.lastname: Wu
authors.forename: M L
authors.initials: ML
authors.lastname: Kashon
authors.forename: K M
authors.initials: KM
authors.lastname: Krajnak
authors.forename: P M
authors.initials: PM
authors.lastname: Wise
authors.forename: L Y
authors.initials: LY
authors.lastname: Lee
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis; D002211:Capsaicin / Q000494:pharmacology; D006168:Guinea Pigs; D017403:In Situ Hybridization; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D011897:Random Allocation; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D012907:Smoking; D015320:Tachykinins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D001549:Benzamides; D010880:Piperidines; D011498:Protein Precursors; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C044206:preprotachykinin; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C073839:SR 48968; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin