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Respir Res. 2010 Oct 7;11:139. doi: 10.1186/1465-9921-11-139.

Expression and function of human hemokinin-1 in human and guinea pig airways.

Author information

1
Laboratory of pulmonary pharmacology UPRES EA220, Foch Hospital, University Versailles-Saint Quentin en Yvelines, 11 rue Guillaume Lenoir, Suresnes, France. s.grassindelyle@gmail.com

Abstract

BACKGROUND:

Human hemokinin-1 (hHK-1) and endokinins are peptides of the tachykinin family encoded by the TAC4 gene. TAC4 and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study.

METHODS:

RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages.

RESULTS:

In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK1-and NK2-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK2-receptors, which blockade unmasked a NK1-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK1-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages.

CONCLUSIONS:

We demonstrate endogenous expression of TAC4 in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.

PMID:
20929541
PMCID:
PMC2959027
DOI:
10.1186/1465-9921-11-139
[Indexed for MEDLINE]
Free PMC Article
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