title: Prevention of extracellular ADP-induced ATP accumulation of the cultured rat spinal astrocytes via P2Y(1)-mediated inhibition of AMPK.
abstract: P2Y(1) is probably an important subtype of purinergic receptors (P2Rs) in modulation of the astrocyte activation in spinal cord. The aim of this study was to observe the effect of P2Y(1) receptor on the abnormal energy metabolism of the cultured rat spinal astrocyte induced by extracellular adenosine diphosphate (ADP). The results showed that adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) in the astrocytes were up-regulated in the presence of ADP, which could be enhanced by MRS2179, a specific antagonist for P2Y(1) receptor. A higher level of expression of the AMP-activated protein kinase (AMPK) was found in the presence of MRS2179 and ADP together than that ADP alone. Blocking of AMPK with Compound C could effectively inhibit the enhancing effect of MRS2179 on ADP-induced astrocyte proliferation and ATP accumulation. Our results suggested that the P2Y(1) receptor mediated inhibition of AMPK may help to prevent the astrocytes from over activation induced by extracellular ADP.
authors: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors: Jian
authors: J
authors: Cui
authors: Shan
authors: S
authors: Ou
authors: Wen-Juan
authors: WJ
authors: He
authors: Lu
authors: L
authors: Du
authors: Yan-Dong
authors: YD
authors: Zhao
authors: Huai-Zhen
authors: HZ
authors: Ruan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058472:Receptors, Purinergic P2Y1 / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D005904:Glial Fibrillary Acidic Protein; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D009419:Nerve Tissue Proteins; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; C030812:adenosine 5'-O-(2-thiodiphosphate); D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases