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Am. J. Respir. Cell Mol. Biol., Volume 25, Number 3, September, 2001 299-305

Chronic Smoking Enhances Tachykinin Synthesis and Airway Responsiveness in Guinea Pigs

Kevin Kwong, Zhong-Xin Wu,* Michael L. Kashon,dagger Kristine M. Krajnak,ddager Phyllis M. Wise, and Lu-Yuan Lee

Department of Physiology, University of Kentucky, Lexington, Kentucky

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 µg/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.

* Present address: Dept. of Anatomy, 4052 HSN, West Virginia University, Morgantown, WV 26506.
dagger Present address: NIOSH, Morgantown, WV 26506.
ddager Present address: Dept. of Biology, West Virginia University, Morgantown, WV 26506.
Abbreviations: airway hyperresponsiveness, AHR; nonmyelinated, C; dynamic lung compliance, Cdyn; calcitonin gene-related peptide, CGRP; cigarette smoke, CS; -like immunoreactivity, -LI; messenger RNA, mRNA; neurokinin, NK; preprotachykinin, PPT; radioimmunoassay, RIA; pulmonary resistance, RL; standard error of the mean, SEM; substance P, SP; saline sodium citrate, SSC.




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