Chronic smoking enhances tachykinin synthesis and airway responsiveness in guinea pigs.
Kwong-K; Wu-ZX; Kashon-ML; Krajnak-KM; Wise-PM; Lee-LY
Am J Respir Cell Mol Biol 2001 Sep; 25(3):299-305
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.
Lung-irritants; Smoking; Laboratory-animals; Animals; Animal-studies; Bronchial-cancer; Cigarette-smoking; Airway-obstruction; Airway-resistance; Exposure-levels; Chronic-exposure; Lung-disease; Lung-disorders; Pulmonary-system-disorders; Respiratory-system-disorders
Lu-Yuan Lee, Ph.D., Dept. of Physiology, MS511A Chandler Medical Center, 800 Rose St., University of Kentucky, Lexington, KY 40536
American Journal Respiratory Cell and Molecular Biology