Initial evidence for the purinergic control of ion/water secretion emerged from studies illustrating that: (a) baseline CFTR activity in Calu-3 lung epithelial cells was blocked by A2BR antagonists [24]; (b) apical addition of adenosine deaminase to primary cultures of naïve human bronchial epithelial (HBE) cells resulted in a CF-like ASL volume depletion [22]; and (c) the ASL height measured in CF HBE cells subjected to shear stress-promoted ATP release is markedly reduced following the addition of the ATPase apyrase [25]. This evidence concerns the gene ADA and cystic fibrosis.