Biologic responses to ATP, ADP, and other extracellular nucleotides are mediated by P2-nucleotide receptors belonging to 2 major classes: G protein-coupled P2Y receptors and nucleotide-gated ion channel P2X receptors. P2RX1 functions as a ligand-gated ion channel with relatively high calcium permeability. Mouse studies suggest that this receptor is essential for normal male reproductive function. The development of selective antagonists for this receptor may provide an effective non-hormonal male contraceptive pill.