Neurokinin A is the predominant tachykinin in human bronchoalveolar lavage fluid in normal and asthmatic subjects

Abstract

Background-Multiple sensory neuropeptides are present in human airways and may contribute to diseases such as asthma. This study quantified and characterised substance P (SP), neurokinin A (NKA), and calcitonin gene related peptide (CGRP) immunoreactivity in bronchoalveolar lavage fluid in asthmatic and normal subjects. Methods-Using specific radioimmunoassay (RIA), SP, NKA and CGRP were measured in bronchoalveolar lavage fluid from asthmatic subjects (n = 5), normal subjects (n = 5), atopic non-asthmatic subjects (n = 6), and asthmatic subjects four hours after allergen challenge (n = 12). Peptide immunoreactivity was characterised using high performance liquid chromatography (HPLC) and RIA. Results-No SP or CGRP immunoreactivity was detected in any of the fractions from samples after extraction, HPLC, and RIA. Non-specific binding resulted in spurious SP immunoreactivity being detected in bronchoalveolar lavage fluid when no extraction process was employed. NKA was detected in significant amounts in asthmatic (median 550, range 425-625 pg/ml) and normal subjects (median 725, range 350-1425 pg/ml). The level of NKA was significantly higher in the asthmatic subjects after allergen challenge (median 750, range 350-1250 pg/ml) than in unchallenged asthmatic subjects (median 600, range 425-600 pg/ml, p<0.01). Conclusions-Extraction and characterisation of peptides from bronchoalveolar lavage fluid must be performed to ensure that the measured immunoreactivity represents target peptide. NKA is present in bronchoalveolar lavage fluid in high concentrations and is the predominant tachykinin. The concentrations of NKA are similar in normal subjects and subjects with mild asthma. (Thorax 1998;53:357-362)

Ozone-Induced Release of Neuropeptides from Human Nasal Mucosa Cells

“…These results are similar to the results of Heaney et al [19], where NKA was found to be the predominant tachykinin in human BALF.…”

“…This leads to the hypothesis that neuropeptides may also be involved. The sensory neuropeptides substance P (SP) and neurokinin A (NKA) are localized in sensory airway nerves, from which they can be released by a variety of stimuli, including allergens and inflammatory mediators [19, 20]. …”

A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma

“…Since Trpa1 Ϫ/Ϫ mice showed clear deficiencies in acute neurogenic peptide release in the airways, we asked whether neuropeptide levels would also be reduced during airway allergen challenge. We compared neuropeptide levels in BALF of OVA-challenged wild-type and Trpa1 Ϫ/Ϫ -deficient C57/BL6 mice, and in antagonist treated Balb/C mice, focusing on NK-A, the most abundant neuropeptide in airway lining fluid (30) (Fig. 4 E and F).…”

The airways pharmacology of DNK333, a potent, selective, non‐peptide dual NK1/NK2 receptor antagonist

“…For instance, SP and NKA are elevated in the lungs of asthmatic patients and the SP concentration is elevated in the sputum of asthmatic patients [Nieber et al, 1992;Heaney et al, 1998;Tomaki et al, 1995]. Furthermore, asthmatics are hyperresponsive to SP, NKA, and bradykinin.…”

“…On the basis of these properties, tachykinins have been implicated in the pathophysiology of airway diseases such as asthma and COPD [Tomaki et al, 1995;Heaney et al, 1998;. DNK333 ((1R,3R,2E)-N-[3, 4-dichlorobenzyl)]-4-[(hexahydro-2-oxo-1H-azepin-3-yl)amino]-N-methyl-3,5 bis(trifluoromethyl) benzamide; Fig.…”