Substance p (nk-1) and neurokinin a (nk-2) receptor gene expression
in inflammatory airway diseases.
Bai, Tony R., Danyi Zhou, Tracey Weir, Blair Walker, Richard Hegele,
Shizu Hayashi, Karen McKay, Gregory P. Bondy, and Tung Fong.
University of British Columbia Pulmonary Research Laboratory, St.
Paul's Hospital, Vancouver, B.C. V6Z 1Y6, Merck Sharpe & Dohme
Research Labs, Rahway, N.J.
APStracts 2:0069L, 1995.
The tachykinin neuropeptides, substance P and neurokinin A have been
postulated to participate in the inflammatory reaction in airways of
smokers and asthmatics. We have examined the hypothesis that the
expression of one or more of the three cloned tachykinin receptors
(NK-1, NK-2, NK-3) is increased in inflammatory airway disorders,
which could result in augmentation of the effect of released
tachykinin neuropeptides. NK-1 receptor and NK-2 receptor but not NK
-3 receptor mRNA were detected by ribonuclease protection assay in RNA
from both cartilaginous and membranous bronchi and subpleural lung.
In lung samples containing membranous airways, NK-2 receptor mRNA
expression was increased 4-fold in asthmatics compared to non-smoking
controls whereas NK-1 receptor mRNA levels were similar in the two
groups. NK-1 and NK-2 receptor mRNA expression was increased 2-fold
in smokers without airflow obstruction compared to non-smokers,
whereas NK-1 receptor mRNA expression was significantly lower in COPD
compared to smoking controls. In situ hybridization indicated NK-1
receptor mRNA was expressed in submucosal glands and airway
epithelial cells whereas NK-2 receptor and NK-3 receptor mRNA were
not detected. These observations have implications for the
pathophysiology and treatment of both asthma and tobacco-smoke
induced airway inflammation.
Received 20 May 1994; accepted in final form 17 April 1995.
APS Manuscript Number L148-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.