Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides

Abstract

Extracellular ATP, at micromolar concentrations, induces significant functional changes in a wide variety of cells and tissues. ATP can be released from the cytosol of damaged cells or from exocytotic vesicles and/or granules contained in many types of secretory cells. There are also efficient extracellular mechanisms for the rapid metabolism of released nucleotides by ecto-ATPases and 5'-nucleotidases. The diverse biological responses to ATP are mediated by a variety of cell surface receptors that are activated when ATP or other nucleotides are bound. The functionally identified nucleotide or P2-purinergic receptors include 1) ATP receptors that stimulate G protein-coupled effector enzymes and signaling cascades, including inositol phospholipid hydrolysis and the mobilization of intracellular Ca2+ stores; 2) ATP receptors that directly activate ligand-gated cation channels in the plasma membranes of many excitable cell types; 3) ATP receptors that, via the rapid induction of surface membrane channels and/or pores permeable to ions and endogenous metabolites, produce cytotoxic or activation responses in macrophages and other immune effector cells; and 4) ADP receptors that trigger rapid ion fluxes and aggregation responses in platelets. Current research in this area is directed toward the identification and structural characterization of these receptors by biochemical and molecular biological approaches.

Molecular cloning and functional expression of a novel rat heart P2X purinoceptor

“…The physiological actions of extracellular ATP have been comprehensively described and include contractile regulation of cardiac, vascular and visceral smooth muscle, excitatory and inhibitory effects on neurons from the central and peripheral nervous system and activation of neuroendocrine secretion (for reviews see [1][2][3]). All these effects are apparently mediated by a miscellaneous group of G-protein coupled receptors (P2Y) and ligand-gated channels (P2X) [4].…”

Desensitization of P2U receptor in neuronal cell line. Different control by the agonists ATP and UTP, as demonstrated by single-cell Ca2+ responses

“…It has important roles as a neurotransmitter in the autonomic system and the central nervous system [1]. Extracellular ATP acts on cell surface receptors in many different cell types by elevating the level of cytosolic Ca# + ([Ca# + ] i ) [1][2][3]. Receptors for extracellular nucleotides have been designated P # receptors (specific for ATP or ADP) and P " receptors (specific for adenosine and AMP).…”

Human neutrophils do not express purinergic P2X7 receptors

“…2′,7′-Dichlorodihydrofluorescein diacetate (DCFH 2 -DA) was obtained from Molecular Probes (Invitrogen, Carlsbad, CA, USA) and 2′,7′-dichlorofluorescein (DCF) from Fluka (Sigma). Reverse transcription polymerase chain reaction (RT-PCR) reagents, SuperScript II reverse transcriptase, oligo(dT) [12][13][14][15][16][17][18] primers, RNAse OUT and Taq DNA Polymerase were purchased from Invitrogen. P2X 7 R antibodies (APR-008, APR-008-F and APR-004) for Western blotting and immunostaining were from Alomone Labs (Jerusalem, Israel).…”

“…In blood, the ATP released by healthy cells in response to stimuli such as shear stress and cell swelling, by damaged cells, by vascular injury or by stimulated platelets, [14,34] is able to stimulate several leukocyte functions such as DNA synthesis, blastogenesis, cell-mediated killing, apoptosis, pro-inflammatory activities, adhesion to endothelial cells, shedding of CD62L and expression of Mac1 [2,28,37,40]. These effects are mediated by purinergic receptors that belong to the metabotropic (P2Y) and/or ionotropic (P2X 1 -P2X 7 ) type [6,25,33].…”