The P2Y GPCRs serve as receptors for extracellular nucleotides. P2Y2 (also known as P2U) is activated by UTP and ATP, and couples to Gq to increase intracellular calcium. The P2Y2 receptor knockout mouse displays defective nucleotide-stimulated Cl-secretion, and a P2Y2 selective agonist increases tracheal epithelial chloride and mucin secretion in dog tracheal epithelium and cultured human airway epithelium, respectively. As a result, P2Y2 is a potential target for treatment of cystic fibrosis. In addition, the P2Y2 KO mouse displays salt-resistant hypertension.