Chronic smoking enhances tachykinin synthesis and airway responsiveness in guinea pigs

K. Kwong, Z. X. Wu, M. L. Kashon, K. M. Krajnak, P. M. Wise, L. Y. Lee

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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 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, β-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.

Original languageEnglish
Pages (from-to)299-305
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume25
Issue number3
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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