Ectonucleoside triphosphate diphosphohydrolase 8 (NTPDase8) (NTPDase8)

Ectonucleoside triphosphate diphosphohydrolase 8 (NTPDase8) is a cell surface-bound enzyme that plays a critical role in regulating extracellular purinergic signaling by hydrolyzing nucleoside triphosphates (ATP, UTP) and diphosphates (ADP, UDP) into their respective monophosphates [UniProt, NIH]. It is primarily expressed on the apical surface of intestinal epithelial cells and the canalicular membranes of hepatocytes [NIH, BenchChem]. In the gut, NTPDase8 acts as a protective factor against inflammation by limiting the activation of P2Y6 receptors by extracellular nucleotides, which are released as danger signals during cell stress [Gut, NIH]. In the liver, it is involved in bile flow regulation and purine salvage [NIH, FASEB J]. Dysregulation of NTPDase8 is associated with inflammatory bowel disease (IBD), liver ischemia-reperfusion injury, and certain cancers, making it a promising therapeutic target for modulating inflammatory and metabolic responses [Gut, NIH, BenchChem]. While no drugs targeting NTPDase8 are currently approved, research into small molecule inhibitors like thiadiazolopyrimidones is ongoing to explore their potential in treating disorders where nucleotide signaling is dysregulated [NIH].

Other names

ENTPD8 [UniProt]Hepatic ATP diphosphohydrolase [NIH]ATPDase [NIH]Canalicular ecto-ATPase [NIH]hATPase [BenchChem]

Inhibition of ectonucleotidase activity to modulate extracellular nucleotide concentrations and P2 receptor activation [NIH].