Our data demonstrate that ethanol affects adenosine-stimulated chloride secretion through CFTR. On epithelial apical surface, adenosine binds to A 2b AR, a predominant adenosine receptor present in airway epithelia [16] . This receptor is coupled to G s protein to activate adenylyl cyclase, which elevates intracellular cAMP and consequently activates PKA. Then, CFTR is phosphorylated by PKA and the channel opens to permeate chloride [40] #. More chloride in ASL will cause less Na + absorption and more water retention, thus increasing ASL height and volume [15, 20] . It is even speculated that adenosine is a sensor for ASL homeostasis. When ASL falls, adenosine levels increase in airways beyond their basal levels and activate A 2B AR and CFTR channels [16, 29] . Our data have linked ethanol-suppression of cAMP levels to attenuation of chloride secretion by airway epithelia. Previous studies have documented that ethanol decreases ciliary beating and epithelial cell migration during wound repair which are associated with compromised cAMP signaling and PKA activation [21, 41] . Moreover, alcohol is reported to upregulate the PDE4 enzyme expression as well as the enzymatic activity in epithelia [22] #, which results in accelerated cAMP degradation. Thus, our data are consistent with the data reported, indicating that alcohol modulates various cellular pathways by reducing cellular cAMP levels.