ADP ribose is an endogenous ligand for the purinergic P2Y1 receptor
2011 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 333, no 1, 8-19 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2011. Vol. 333, no 1, 8-19 p.
Calcium, Cell signaling, ADPr, Purinergic receptors, TRPM2
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-148592DOI: 10.1016/j.mce.2010.11.004ISI: 000287283900002PubMedID: 21094205OAI: oai:DiVA.org:uu-148592DiVA: diva2:402543
Correction in: Molecular and Cellular Endocrinology, 2011, vol. 337, issue. 1-2, p. 122-123, doi: 10.1016/j.mce.2011.02.0082011-03-082011-03-082013-03-01Bibliographically approved