کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2196620 | 1098837 | 2011 | 12 صفحه PDF | دانلود رایگان |
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 β-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 ADPr-induced [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.
Journal: Molecular and Cellular Endocrinology - Volume 333, Issue 1, 10 February 2011, Pages 8–19