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

  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},
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.
Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System
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.
Airway Epithelial Cell Release of GABA is Regulated by Protein Kinase A
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.
A novel role of intestine epithelial GABAergic signaling in regulating intestinal fluid secretion.
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
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.
Smoking-mediated up-regulation of GAD67 expression in the human airway epithelium
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.
Prenatal nicotine exposure increases GABA signaling and mucin expression in airway epithelium.
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.
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
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
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.


GABAergic Mechanisms in Epilepsy
Summary: γ‐Aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tone that counterbalances neuronal excitation. When this balance is
Differential expression of GABAA receptor π subunit in cultured rat alveolar epithelial cells
The results suggest that GABRP expression is differentially regulated by culture substrata, growth factor, detached gel, and an air-apical surface.
Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma
The results demonstrate the importance of direct effects of IL-13 on epithelial cells in causing two central features of asthma, including airway hyperreactivity and mucus overproduction.
A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma
It is shown that the intratracheal instillation of this peptide blocks mucus hypersecretion in a mouse model of asthma, and a pivotal role for MARCKS protein, specifically its N-terminal region, in modulating this secretory process in mammalian airways is supported.
Interleukin-1beta enhances GABAA receptor cell-surface expression by a phosphatidylinositol 3-kinase/Akt pathway: relevance to sepsis-associated encephalopathy.
Clinical and experimental evidence that this brain dysfunction may be related to altered neurotransmission produced by inflammatory mediators is presented and it is proposed that through this mechanism IL-1beta might alter synaptic strength at central GABAergic synapses and so contribute to the cognitive dysfunction observed in SAE.
Epithelial-mesenchymal communication in the pathogenesis of chronic asthma.
The observation that structural changes in the airways in children at or before the onset of asthma occurs irrespective of inflammation might suggest that premodeling is required before Th-2 inflammatory responses can be sustained.
Epidermal growth factor system regulates mucin production in airways.
Goblet-cell hyperplasia is a critical pathological feature in hypersecretory diseases of airways. However, the underlying mechanisms are unknown, and no effective therapy exists. Here we show that
Excessive Expression of Acetylcholinesterase Impairs Glutamatergic Synaptogenesis in Hippocampal Neurons
It is found that AChE was highly expressed in cultured embryonic hippocampal neurons at early culture days, particularly in dendritic compartments including the growth cone, and interference with the nonenzymatic features of A cholinesterase alters A cholinergic expression, which impairs excitatory synaptic structure and functions.
Goblet cell and mucin gene abnormalities in asthma.
The process of working out the molecular mechanisms of GCH and goblet cell degranulation should provide new targets for novel therapeutic interventions, because mucus hypersecretion is an important cause of morbidity and mortality in patients with asthma, and no specific treatments are available.
The GABAA receptor gene family: new opportunities for drug development.
  • P. Whiting
  • Biology, Chemistry
    Current opinion in drug discovery & development
  • 2003
This review will primarily focus on progress achieved in the understanding of the function of this GABAA receptors, and potential exploitation for drug development.