ADP ribose is an endogenous ligand for the purinergic P2Y1 receptor

A.J. Gustafsson, L. Muraro, C. Dahlberg, Marie Migaud, Olivier Chevallier, H.N. Khanh, K. Krishnan, Xiaolin Li, Barira Islam

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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. (c) 2010 Elsevier Ireland Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)8-19
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume333
Issue number1
DOIs
Publication statusPublished - 10 Feb 2011

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

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