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A GABAergic system in airway epithelium is essential for mucus overproduction in asthma.

Abstract：

:Gamma-aminobutyric acid (GABA) is an important neurotransmitter that, through the subtype A GABA receptor (GABAAR), induces inhibition in the adult brain. Here we show that an excitatory, rather than inhibitory, GABAergic system exists in airway epithelial cells. Both GABAARs and the GABA synthetic enzyme glutamic acid decarboxylase (GAD) are expressed in pulmonary epithelial cells. Activation of GABAARs depolarized these cells. The expression of GAD in the cytosol and GABAARs in the apical membranes of airway epithelial cells increased markedly when mice were sensitized and then challenged with ovalbumin, an approach for inducing allergic asthmatic reactions. Similarly, GAD and GABAARs in airway epithelial cells of humans with asthma increased after allergen inhalation challenge. Intranasal application of selective GABAAR inhibitors suppressed the hyperplasia of goblet cells and the overproduction of mucus induced by ovalbumin or interleukin-13 in mice. These findings show that a previously unknown epithelial GABAergic system has an essential role in asthma.

journal_name

Nat Med

journal_title

Nature medicine

authors

Xiang YY,Wang S,Liu M,Hirota JA,Li J,Ju W,Fan Y,Kelly MM,Ye B,Orser B,O'Byrne PM,Inman MD,Yang X,Lu WY

doi

10.1038/nm1604

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

862-7

issue

7

eissn

1078-8956

issn

1546-170X

pii

nm1604

journal_volume

13

pub_type

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