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.
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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.
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The intestinal GABAergic signaling becomes intensified in allergic diarrhea, and inhibition of this GABA-signal system alleviates the allergic diarrhea.
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.
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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.
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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.
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.
Endogenous &ggr;-Aminobutyric Acid Modulates Tonic Guinea Pig Airway Tone and Propofol-induced Airway Smooth Muscle Relaxation
TLDR
These studies demonstrate that GABA is endogenously present and increases after contractile stimuli in guinea pig upper airways and that endogenous GABA contributes a tonic prorelaxant component in the maintenance of airway smooth muscle tone.
Functional Expression of g –Amino Butyric Acid Transporter 2 in Human and Guinea Pig Airway Epithelium and Smooth Muscle
TLDR
Theyalsoprovide a mechanism by which locally synthesized GABA can be released from cells into the airway to activate GABA A channels and GABA B receptors, with subsequent autocrine and/or paracrine signaling effects on airway epithelium and ASM.
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