Ectonucleoside triphosphate diphosphohydrolase 3 (NTPDase3) (NTPDase3)

Ectonucleoside triphosphate diphosphohydrolase 3 (E-NTPDase3), also known as CD39L3, is a cell-surface enzyme that plays a critical role in purinergic signaling by hydrolyzing extracellular nucleotides [1, 2]. It primarily converts adenosine triphosphate (ATP) and adenosine diphosphate (ADP) into adenosine monophosphate (AMP), thereby regulating the availability of ligands for P2 purinergic receptors [4, 6]. E-NTPDase3 is highly expressed in pancreatic beta cells, where it modulates glucose-induced insulin secretion; inhibition of the enzyme leads to increased extracellular ATP levels and enhanced insulin release [4, 11]. Beyond the pancreas, it is found in the brain, where it may influence sleep-wake behavior and synaptic function, as well as in the heart and gastrointestinal tract [4, 5, 10]. In disease contexts, E-NTPDase3 is considered a potential target for treating type 2 diabetes and obesity, as its inhibition or deletion has been shown to improve glucose tolerance and resistance to diet-induced obesity [6, 14]. It also serves as a highly specific biomarker for identifying and imaging pancreatic beta cells in both healthy and diabetic states [5, 11]. While no clinical drugs currently target E-NTPDase3, research inhibitors like ARL 67156 and POM-1 are used to study its therapeutic potential in metabolic and inflammatory disorders [6, 7].

Other names

CD39L3HB6ENTPD3Ecto-ATP diphosphohydrolase 3Ecto-apyrase 3E-NTPDase3

Inhibition of extracellular ATP and ADP hydrolysis to enhance purinergic receptor activation and modulate downstream signaling pathways such as insulin secretion [6, 14].