Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) is the dominant ectonucleotidase expressed by rat astrocytes

• Published in: Neuroscience 2006, Vol.138 (2), p.421-432
• Main Authors: Wink, M.R., Braganhol, E., Tamajusuku, A.S.K., Lenz, G., Zerbini, L.F., Libermann, T.A., Sévigny, J., Battastini, A.M.O., Robson, S.C.
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - metabolism; Animals; astrocytes; Astrocytes - enzymology; ATP; Biological and medical sciences; Brain - enzymology; CD39L1; E-NTPDase family; ecto-ATPase; Fundamental and applied biological sciences. Psychology; Kinetics; NTPDase2; Rats; Recombinant Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Substrate Specificity; Transfection; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2005.11.039

Inflammatory and degenerative pathophysiological processes within the CNS are important causes of human disease. Astrocytes appear to modulate these reactions and are a major source of inflammatory mediators, e.g. extracellular adenine nucleotides, in nervous tissues. Actions following extracellular nucleotides binding to type 2 purinergic receptors are regulated by ectonucleotidases, including members of the CD39/ecto-nucleoside triphosphate diphosphohydrolase family. The ectonucleotidases of astrocytes expressed by rat brain rapidly convert extracellular ATP to ADP, ultimately to AMP. RT-PCR, immunocytochemistry as well as Western blotting analysis demonstrated expression of multiple ecto-nucleoside triphosphate diphosphohydrolase family members at both the mRNA and protein level. By quantitative real-time PCR, we identified Entpd2 ( CD39L1) as the dominant Entpd gene expressed by rat hippocampal, cortical and cerebellar astrocytes. These data in combination with the elevated ecto-ATPase activity observed in these brain regions, suggest that NTPDase2, an ecto-enzyme that preferentially hydrolyzes ATP, is the major ecto-nucleoside triphosphate diphosphohydrolase expressed by rat astrocytes. NTPDase2 may modulate inflammatory reactions within the CNS and could represent a useful therapeutic target in human disease.