ADP ribose is an endogenous ligand for the purinergic P2Y1 receptor

作者：Gustafsson Amanda Jabin^*; Muraro Lucia; Dahlberg Carin; Migaud Marie; Chevallier Olivier; Khanh Hoa Nguyen; Krishnan Kalaiselvan; Li Nailin; Islam Md Shahidul

来源：Molecular and Cellular Endocrinology, 2011, 333(1): 8-19.

DOI：10.1016/j.mce.2010.11.004

• Calcium
• Cell signaling
• ADPr
• Purinergic receptors
• TRPM2

The mechanism by which extracellular ADP ribose (ADPr) increases intracellular free Ca2+ concentration ([Ca2+](i)) remains unknown. We measured [Ca2+](i) changes in fura-2 loaded rat insulinoma INS-1E cells, and in primary beta-cells from rat and human. A phosphonate analogue of ADPr (PADPr) and 8-Bromo-ADPr (8Br-ADPr) were synthesized. ADPr increased [Ca2+](i) in the form of a peak followed by a plateau dependent on extracellular Ca2+. NAD(+), cADPr, PADPr, 8Br-ADPr or breakdown products of ADPr did not increase [Ca2+](i). The ADPr-induced [Ca2+](i) increase was not affected by inhibitors of TRPM2, but was abolished by thapsigargin and inhibited when phospholipase C and IP3 receptors were inhibited. MRS 2179 and MRS 2279, specific inhibitors of the purinergic receptor P2Y1, completely blocked the ADPrinduced [Ca2+](i) increase. ADPr increased [Ca2+](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.

• 出版日期2011-2-10