Type 2 purinergic receptors and extracellular ATP metabolism. Extracellular ATP exerts its effects on cells by binding to type 2 purinergic receptors. A prototypic P2X receptor is shown. In the active conformation, 3 peptide subunits are assembled to form an ion-permeable channel pore. Each one of the subunits is formed by 2 membrane-spanning domains, a large extracellular loop, and intracellular carboxyl and amino termini. Binding of ATP is crucial for subunit oligomerization, which leads to the opening of pores and the determination of the influx/efflux of cations. ATP can bind P2Y receptors, which are 7 membrane-spanning, G-protein–coupled receptors. Binding of nucleotides induces different cascades of intracellular signaling events, depending on the specific type of G protein associated with the receptor (P2Y1, 6, 14: G_q/11; P2Y2, 4: G_q/11-G_i; P2Y11: G_s, G_q/11; P2Y12, 13: G_i/o). ATP in the extracellular space is metabolized by the plasma membrane-bound ectoenzyme CD39 that catalyzes the hydrolysis of ATP into ADP/AMP and CD73, which subsequently hydrolyzes AMP into adenosine. The activity of these enzymes contributes to the removal of ATP from the extracellular space, thus limiting the duration of signaling. In turn, adenosine engages purinergic P1 receptors (adenosine receptors).