ADP ribose is an endogenous ligand for the purinergic P2Y1 receptor
| Autor: | Nailin Li, Md. Shahidul Islam, Carin I. M. Dahlberg, Hoa Nguyen Khanh, Marie E. Migaud, Kalaiselvan Krishnan, Lucia Muraro, Amanda Jabin Gustafsson, Olivier P. Chevallier |
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| Rok vydání: | 2010 |
| Předmět: |
Agonist
Thapsigargin Halogenation medicine.drug_class Biology Ligands Biochemistry chemistry.chemical_compound Receptors Purinergic P2Y1 Endocrinology Cell Line Tumor Insulin-Secreting Cells Extracellular medicine Animals Humans Inositol 1 4 5-Trisphosphate Receptors TRPM2 Receptor Molecular Biology Cells Cultured Adenosine Diphosphate Ribose Phospholipase C Purinergic receptor Molecular biology Rats Adenosine Diphosphate chemistry Type C Phospholipases Purinergic P2Y Receptor Antagonists Calcium NAD+ kinase Purinergic P2Y Receptor Agonists |
| Zdroj: | Molecular and cellular endocrinology. 333(1) |
| ISSN: | 1872-8057 |
| Popis: | The mechanism by which extracellular ADP ribose (ADPr) increases intracellular free Ca(2+) concentration ([Ca(2+)](i)) remains unknown. We measured [Ca(2+)](i) changes in fura-2 loaded rat insulinoma INS-1E cells, and in primary β-cells from rat and human. A phosphonate analogue of ADPr (PADPr) and 8-Bromo-ADPr (8Br-ADPr) were synthesized. ADPr increased [Ca(2+)](i) in the form of a peak followed by a plateau dependent on extracellular Ca(2+). NAD(+), cADPr, PADPr, 8Br-ADPr or breakdown products of ADPr did not increase [Ca(2+)](i). The ADPr-induced [Ca(2+)](i) increase was not affected by inhibitors of TRPM2, but was abolished by thapsigargin and inhibited when phospholipase C and IP(3) receptors were inhibited. MRS 2179 and MRS 2279, specific inhibitors of the purinergic receptor P2Y1, completely blocked the ADPr-induced [Ca(2+)](i) increase. ADPr increased [Ca(2+)](i) in transfected human astrocytoma cells (1321N1) that express human P2Y1 receptors, but not in untransfected astrocytoma cells. We conclude that ADPr is a specific agonist of P2Y1 receptors. |
| Databáze: | OpenAIRE |
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