P2Y receptors are members of a large family of G protein-coupled receptors that is classified into five functionally characterized human gene products (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11). The P2Y2 receptor, originally called P2U purinoceptor, recognizes both ATP and UTP as the most potent agonists. It ranges from excitation of sympathetic neurons, muscle cell proliferation, endothelial cell adhesion, and spermiogenesis to acid-base equilibrium in intestinal epithelial cells and mucociliary clearance in normal and cystic fibrosis airway epithelia. In the airways, the P2Y2 and the P2Y6 receptors on the apical surface of airway epithelial cells control several of the calcium and protein kinase C dependent components of mucociliary clearance. The P2Y2 receptor is also expressed on the basolateral cell surface along with the P2Y1 receptor.