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Purinergic Signal. 2018 Jun;14(2):157-166. doi: 10.1007/s11302-018-9601-z. Epub 2018 Mar 7.

NPP1 is responsible for potent extracellular ATP hydrolysis as NTPDase1 in primary cultured murine microglia.

Author information

1
Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea.
2
Department of Pharmacology and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-752, Republic of Korea. jooyoungkim@yuhs.ac.

Abstract

The movement of microglia is regulated mainly by P1 and P2 purinergic receptors, which are activated by various nucleotides and their metabolites. Recently, such purinergic signalling has been spotlighted because of potential roles in the pathophysiologies of neurodegenerative and neuropsychiatric disorders. To understand the characteristics of microglia in relation of P1 and P2 signalling, we investigated the ectoenzymes expressed in microglia. At first, we profiled the expression of all known ectoenzymes in cultured microglia. We found that, like NTPDase1 (ectonucleoside triphosphate diphosphohydrolase 1, CD39), NPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1, PC-1) is also highly expressed in primary cultured murine microglia. Knockdown of NPP1 significantly reduced ATP hydrolysis and Pi production in cultured microglia. In addition, the knockdown of NPP1 enhanced basal nucleotide-stimulating responses of cultured microglia, such as phagocytosis and cell migration, and these results were very similar to NTPDase1 knockdown results. Moreover, inhibition of the adenosine receptors by caffeine treatment reduced phagocytosis of NPP1 knock downed-cultured microglia. In conclusion, we suggest that these potent ectoenzymes of primary cultured murine microglia, NPP1 together with CD73 (ecto-5'-nucleotidase) maintain the adenosine levels for triggering nucleotide-stimulating responses.

KEYWORDS:

Ectoenzyme; Microglia; Migration; NPP1; NTPDase1; Phagocytosis

PMID:
29516286
PMCID:
PMC5940628
DOI:
10.1007/s11302-018-9601-z
[Indexed for MEDLINE]
Free PMC Article

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