title: Impaired P2X and P2Y receptor-mediated signaling in HPRT-deficient B103 neuroblastoma cells.
abstract: Defect of hypoxanthine phosphoribosyl transferase (HPRT) causes Lesch-Nyhan disease (LND), but the link between HPRT deficiency and the self-injurious behavior of LND is unknown. In a previous study (Pinto et al., J. Neurochem. 72 (2005) 1579-1586) we reported on a decrease in nucleotidase activity in membranes of several HPRT(-) cell lines and fibroblasts from LND patients. Since nucleotidases are involved in ATP-induced signal transduction, in the present study, we tested the hypothesis that P2X and P2Y receptor-mediated signal transduction is impaired in HPRT deficiency. As model we studied rat B103 neuroblastoma cells. Compared to control cells, in HPRT(-) cells, NTP and NDP-induced Ca(2+) influx across the membrane and Ca(2+) mobilization from intracellular stores were impaired. Both P2X and P2Y receptors were involved in the responses. Quantitative real-time PCR revealed reduced expression of receptors P2X(3), P2X(5), P2Y(2), P2Y(4), P2Y(12), P2Y(13) and P2Y(14) in HPRT deficiency. Collectively, HPRT deficiency is associated with abnormal purinergic signaling, encompassing P2X and P2Y receptors and nucleotidases.
authors: Department of Pharmacology and Toxicology, Institute of Pharmacy, University of Regensburg, Germany.
authors: Miriam
authors: M
authors: Erdorf
authors: Juliane
authors: J
authors: von der Ohe
authors: Roland
authors: R
authors: Seifert
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor / Q000502:physiology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency*; D007926:Lesch-Nyhan Syndrome; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009711:Nucleotides / Q000494:pharmacology; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D058469:Receptors, Purinergic P2X / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D058470:Receptors, Purinergic P2Y / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016728:Self-Injurious Behavior; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D009711:Nucleotides; D058469:Receptors, Purinergic P2X; D058470:Receptors, Purinergic P2Y; D007041:Hypoxanthine Phosphoribosyltransferase