Nucleotide receptors

Adenosine 5′-triphosphate (ATP) and/or related nucleotides act at both ionotrophic (P2X) and metabotropic (P2Y) receptors. P2X receptors subunits (P2X 1—P2X 7) form ligand-gated cation channels, as homomultimers or heteromultimers. Recent work indicates that P2X 3 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. P2X 7 subunits from 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 Ca 2+ 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.