Chronic smoking enhances tachykinin synthesis and airway responsiveness in guinea pigs

Am J Respir Cell Mol Biol. 2001 Sep;25(3):299-305. doi: 10.1165/ajrcmb.25.3.4557.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzamides / pharmacology
  • Bronchi / drug effects
  • Bronchi / innervation*
  • Bronchi / physiology
  • Bronchial Hyperreactivity / physiopathology*
  • Calcitonin Gene-Related Peptide / biosynthesis
  • Capsaicin / pharmacology
  • Guinea Pigs
  • In Situ Hybridization
  • Male
  • Neurons, Afferent / physiology*
  • Piperidines / pharmacology
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Radioimmunoassay
  • Random Allocation
  • Receptors, Neurokinin-2 / antagonists & inhibitors
  • Smoking*
  • Tachykinins / biosynthesis*
  • Tachykinins / genetics
  • Tachykinins / metabolism

Substances

  • Benzamides
  • Piperidines
  • Protein Precursors
  • Receptors, Neurokinin-2
  • Tachykinins
  • preprotachykinin
  • 3-(2-methoxybenzylamino)-2-phenylpiperidine
  • SR 48968
  • Calcitonin Gene-Related Peptide
  • Capsaicin