Signal transduction by P2-purinergic receptors for extracellular ATP.
Extracellular adenosine triphosphate (ATP), at micromolar/nanomolar concentrations, has been shown to induce significant functional changes in a wide variety of normal and transformed cell types. While ATP can be nonspecifically released from the cytosol of damaged cells, it is also co-packaged in certain exocytotic vesicles/granules containing conventional neurotransmitters and hormones. The diverse biologic responses to ATP appear to be mediated by a variety of so-called P2-purinergic, cell surface receptors that are activated upon binding ATP and other nucleotides. Recent physiologic, biochemical, and pharmacologic studies suggest that there are multiple ATP receptor subtypes. These include: (1) G-protein-coupled ATP receptors, which stimulate inositol phospholipid hydrolysis, Ca2+ mobilization, and activation of protein kinase C; (2) ATP receptors that directly activate nonselective cation channels in the plasma membranes of a variety of excitable cell types; and (3) ATP receptors that, via the rapid induction of surface membranes pores permeable to both ions and endogenous metabolites, can produce cytotoxic or activation responses in T lymphocytes and other immune effector cells. In addition to these functional criteria, these putative ATP receptor subtypes can be distinguished by characteristic selectivities for a variety of structurally modified ATP analogs. Current research is directed towards the identification, isolation, and structural characterization of these receptors by both biochemical and molecular biologic approaches.
Dubyak
G R
GR
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, 44106.
D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism; D007473:Ion Channels / Q000502:physiology; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D011983:Receptors, Purinergic / Q000378:metabolism*; D015398:Signal Transduction; D009435:Synaptic Transmission
C037688:ADP-ATP carrier receptor; D007473:Ion Channels; D018160:Receptors, Cytoplasmic and Nuclear; D011983:Receptors, Purinergic; D000226:Mitochondrial ADP, ATP Translocases; D010727:Phosphoric Diester Hydrolases; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase