Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM2

Title: ADP ribose is an endogenous ligand for the purinergic P2Y1 receptor.

Authors: Amanda Jabin Gustafsson, Lucia Muraro, Carin Dahlberg, Marie Migaud, Olivier Chevallier, Hoa Nguyen Khanh, Kalaiselvan Krishnan, Nailin Li, Md Shahidul Islam

Journal, date & volume: Mol. Cell. Endocrinol., 2011 Feb 10 , 333, 8-19

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21094205

Abstract
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.