Based on the data that ethanol impairs the adenosine-activated chloride secretion by reducing the cellular cAMP level, we chose to block endogenous cAMP degradation pharmacologically to counteract the alcohol-suppressive effect on chloride secretion. Air-liquid interface cultures of Calu-3 cells were similarly exposed to ethanol for 24 hours and treated with 100 mM of non-specific phosphodiesterase inhibitor IBMX along with adenosine stimulation. The data in Figure 6 indicate that IBMX almost completely restored the ethanol suppression of Calu-3 chloride secretion (p,0.05, n = 4). Papaverine is a clinically used phosphodiesterase inhibitor. This drug also overcame the inhibitory effect of ethanol on adenosine-induced transepithelial chloride conductance (p,0.05, n = 4) (Fig. 6) . These results not only confirm that ethanol modulates adenosine-cAMP signaling but also suggest that phosphodiesterase inhibitors may be useful as the potential therapeutic agents for improving the airway epithelial ion transport and mucociliary clearance in alcoholic patients.