Prevention of extracellular ADP-induced ATP accumulation of the cultured rat spinal astrocytes via P2Y(1)-mediated inhibition of AMPK

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.

► Extracellular ADP increased ATP biosynthesis in the cultured rat spinal astrocytes.
► The P2Y(1) receptor acted as an inhibitor in the ADP-induced ATP accumulation.
► AMPK may be involved in the modulation of the ADP-induced ATP accumulation.
► Blocking of AMPK could effectively inhibit ADP-induced astrocyte proliferation and ATP accumulation.