Nucleotide receptors.

Adenosine 5'-triphosphate (ATP) and/or related nucleotides act at both ionotropic (P2X) and metabotropic (P2Y) receptors. P2X receptor subunits (P2X1-P2X7) form ligand-gated cation channels, as homomultimers or heteromultimers. Recent work indicates that P2X3 subunits participate in channels expressed by nociceptive sensory neurons, and that the second of the two transmembrane domains of each subunit contributes to the ion permeation pathway. P2X7 subunits form large cytolytic pores in addition to cation channels; they have been found in macrophages and brain microglia. P2Y receptors form a distinct subset of G-protein-coupled receptors; most couple through G proteins to phospholipase C, but inhibition of adenylate cyclase and N-type Ca2+ channels, and activation of K+ channels also occurs. Expressed P2Y receptors have generally been distinguished pharmacologically by the rank order of effectiveness of agonists; some prefer pyrimidines to purines. Recent studies suggest that it is important to use purified nucleotides in such classifications. Several P2Y receptors have a very widespread tissue distribution.