Contribution of P2X7 receptors to adenosine uptake by cultured mouse astrocytes

Glia
Hiroto OkudaKazuki Nagasawa

Abstract

Nucleotides and nucleosides play important roles by maintaining brain homeostasis, and their extracellular concentrations are mainly regulated by ectonucleotidases and nucleoside transporters expressed by astrocytes. Extracellularly applied NAD(+) prevents astrocyte death caused by excessive activation of poly(ADP-ribose) polymerase-1, of which the molecular mechanism has not been fully elucidated. Recently, exogenous NAD(+) was reported to enter astrocytes via the P2X7 receptor (P2X7R)-associated channel/pore. In this study, we examined whether the intact form of NAD(+) is incorporated into astrocytes. A large portion of extracellularly added NAD(+) was degraded into metabolites such as AMP and adenosine in the extracellular space. The uptake of adenine ring-labeled [(14)C]NAD(+), but not nicotinamide moiety-labeled [(3)H]NAD(+), showed time- and temperature-dependency, and was significantly enhanced on addition of apyrase, and was reduced by 8-Br-cADPR and ARL67156, inhibitors of CD38 and ectoapyrase, respectively, and P2X7R knockdown, suggesting that the detected uptake of [(14)C]NAD(+) resulted from [(14)C]adenosine acting as a metabolite of [(14)C]NAD(+). Pharmacological and genetic inhibition of P2X7R with brilliant blue ...Continue Reading

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Citations

May 10, 2012·Experimental Neurology·Shigeki Tsutsui, Peter K Stys
Dec 11, 2013·Translational Stroke Research·Katrina OwensTibor Kristian
Apr 6, 2012·Neurochemical Research·Franziska Wilhelm, Johannes Hirrlinger
Jul 11, 2012·Journal of Neurochemistry·Kentaro NishidaKazuki Nagasawa
Aug 21, 2013·Biochemical and Biophysical Research Communications·Mina YamamotoKazuki Nagasawa
Mar 24, 2021·Cellular and Molecular Life Sciences : CMLS·Massimiliano GasparriniNadia Raffaelli

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