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

@article{Xiang2007AGS,
  title={A GABAergic system in airway epithelium is essential for mucus overproduction in asthma},
  author={Y Y Xiang and Shuhe Wang and Mingyao Liu and Jeremy A. Hirota and Jingxin Li and William Ju and Yijun Fan and Margaret M. Kelly and Bin Ye and Beverley A. Orser and Paul M. O'Byrne and Mark D. Inman and Xi Yang and Wei-yang Lu},
  journal={Nature Medicine},
  year={2007},
  volume={13},
  pages={862-867}
}
γ-Aminobutyric acid (GABA) is an important neurotransmitter that, through the subtype A GABA receptor (GABAAR), induces inhibition in the adult brain. [...] Key Result 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.Expand
Functional expression of γ-amino butyric acid transporter 2 in human and guinea pig airway epithelium and smooth muscle.
TLDR
Results demonstrate that two isoforms of GATs, but not VGAT, are expressed in both airway epithelial and smooth muscle cells, and provide a mechanism by which locally synthesized GABA can be released from these cells into the airway to activate GABA(A) channels and GABA(B) receptors, with subsequent autocrine and/or paracrine signaling effects onAirway epithelium and ASM. Expand
Pulmonary Neuroendocrine Cells Secrete γ-Aminobutyric Acid to Induce Goblet Cell Hyperplasia in Primate Models.
TLDR
An evolutionarily conserved intraepithelial GABA signaling that, in concert with IL-13, plays an essential role in mucus overproduction is demonstrated. Expand
Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System
TLDR
It is reported that luteolin, a natural flavonoid compound, suppresses mucus overproduction by functionally inhibiting the GABAergic system, suggesting the potential for therapeutic administration of lutesin in the treatment of mucusOverproduction in asthma patients. Expand
Airway Epithelial Cell Release of GABA is Regulated by Protein Kinase A
TLDR
β-agonist pretreatment prior to methacholine challenge attenuated in vivo GABA release in mouse BAL and 3H-GABA release from depolarized BEAS-2B cells, indicating β-agonists decrease GABA release from airway epithelium through the activation of cAMP and PKA. Expand
Functional expression of GABAB receptors in airway epithelium.
TLDR
GA may modulate an uncharacterized signaling cascade via GABA(B) receptors coupled to G(i) protein in airway epithelium and cross-regulate the phospholipase C/inositol phosphate pathway. Expand
A novel role of intestine epithelial GABAergic signaling in regulating intestinal fluid secretion.
TLDR
The intestinal GABAergic signaling becomes intensified in allergic diarrhea, and inhibition of this GABA-signal system alleviates the allergic diarrhea. Expand
Expression of GABAergic system in pulmonary neuroendocrine cells and airway epithelial cells in GAD67-GFP knock-in mice
TLDR
It is demonstrated that PNECs in theAirway epithelium have a GABA production system and indicated that GABA plays functional roles in airway epithelial cells through GABAB receptors. Expand
Smoking-mediated up-regulation of GAD67 expression in the human airway epithelium
TLDR
The correlation of GAD67 gene expression with MUC5AC expressions suggests that the up-regulation of airway epithelium expression of G AD67 may contribute to the increase in mucus production observed in association with cigarette smoking. Expand
Prenatal nicotine exposure increases GABA signaling and mucin expression in airway epithelium.
TLDR
A new mechanism linking smoking with the increased mucin seen in asthma and chronic obstructive pulmonary disorder is provided, and a new paradigm of communication between non-neuronal transmitter systems in BECs is suggested. Expand
Airway epithelium is a predominant source of endogenous airway GABA and contributes to relaxation of airway smooth muscle tone.
TLDR
Airway epithelium is a predominant cellular source of endogenous GABA in the airway and contributes significant prorelaxant GABA effects on airway smooth muscle force. Expand
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