Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in inflammatory airway diseases.
The tachykinin neuropeptides substance P and neurokinin (NK) 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 (NK1, NK2, and NK3) is increased in inflammatory airway disorders, which could result in augmentation of the effect of released tachykinin neuropeptides. NK1 receptor and NK2 receptor but not NK3-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, NK2-receptor mRNA expression was increased fourfold in asthmatics compared with nonsmoking controls, whereas NK1-receptor mRNA levels were similar in the two groups. NK1- and NK2-receptor mRNA expression was increased twofold in smokers without airflow obstruction compared with nonsmokers, whereas NK1-receptor mRNA expression was significantly lower in patients with chronic obstructive pulmonary disease compared with smoking controls. In situ hybridization indicated NK1-receptor mRNA was expressed in submucosal glands and airway epithelial cells, whereas NK2-receptor and NK3-receptor mRNA were not detected. These observations have implications for the pathophysiology and treatment of both asthma and tobacco smoke-induced airway inflammation.
Bai
T R
TR
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver.
Zhou
D
D
Weir
T
T
Walker
B
B
Hegele
R
R
Hayashi
S
S
McKay
K
K
Bondy
G P
GP
Fong
T
T
D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics*; D001254:Astrocytoma / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008173:Lung Diseases, Obstructive / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics*; D018041:Receptors, Neurokinin-2 / Q000235:genetics*; D018039:Receptors, Tachykinin / Q000235:genetics; D012260:Ribonucleases; D012907:Smoking; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018039:Receptors, Tachykinin; D012260:Ribonucleases