Abstract:

Objective    To explore the role of γ-amino-butyric acid (GABA) in lung epithelial cell proliferation. MethodsExpressions of GAD65/67 and GABAAR were identified by immunohistochemistry and confocal microscopy. The GABA-induced current was measured by whole cell patch clamp technique. The effect of GABA on cell proliferation was investigated by BrdU-ELISA and cell-counting assay. Results     GAD65/67 and GABAAR were localized in the airway epithelium and lung epithelial cell line A549 cells. In addition, the GABA-induced current was markedly increased in lung epithelial cells during mitosis. Further study showed that GABA induced lung epithelial cell proliferation in a GABAA receptor (GABAAR)- dependent manner. Voltage-dependent calcium channels were also involved in GABA-induced cell proliferation. Conclusion     The GABAergic signal system can regulate lung epithelial cell proliferation in an auto/paracrine manner, through GABAAR inducing cell membrane depolarization, opening voltage-dependent calcium channels and increasing cytoplasmic calcium. This finding may provide a new strategy for the treatment of lung cancer or lung epithelial injury.

Key words: γ-amino-butyric acid; GABAA receptor; Lung epithelial cells; Proliferation