apyrase and Liver-Diseases

Extracellular adenosine triphosphate (ATP) is a danger signal released by dying and damaged cells, and it functions as an immunostimulatory signal that promotes inflammation. The ectonucleotidases CD39/ectonucleoside triphosphate diphosphohydrolase-1 and CD73/ecto-5'-nucleotidase are cell-surface enzymes that breakdown extracellular ATP into adenosine. This drives a shift from an ATP-driven proinflammatory environment to an anti-inflammatory milieu induced by adenosine. The CD39-CD73-adenosine pathway changes dynamically with the pathophysiological context in which it is embedded. Accumulating evidence suggests that CD39 and CD73 play important roles in liver disease as critical components of the extracellular adenosinergic pathway. Recent studies have shown that the modification of the CD39-CD73-adenosine pathway alters the liver's response to injury. Moreover, adenosine exerts different effects on the pathophysiology of the liver through different receptors. In this review, we aim to describe the role of the CD39-CD73-adenosine pathway and adenosine receptors in liver disease, highlighting potential therapeutic targets in this pathway, which will facilitate the development of therapeutic strategies for the treatment of liver disease.

Topics: 5'-Nucleotidase; Adenosine; Adenosine Triphosphate; Animals; Antigens, CD; Apyrase; Humans; Liver Diseases; Signal Transduction

Purinergic signaling has been postulated as a mechanism of cellular signaling since the early 1970s. Cellular responses triggered by extracellular nucleotides and nucleosides occur by defined adenosine (P1) and ATP (P2) receptors, respectively, and play a prominent role in many aspects of health and disease, including those involving the liver. In normal physiology, extracellular nucleotides modulate many of the normal biologic and hepatic metabolic processes such as gluconeogenesis and insulin responsiveness. Further, in multiple disease states, ATP and certain nucleotides serve as danger signals and are involved in heightened purinergic receptor activation in a myriad of pathologic processes. Recently, others and we have shown the regulation of purinergic signaling by ectonucleotidases to play an important role in the acute vascular pathobiology of liver inflammation, regeneration, and immunity, as in ischemia reperfusion and transplantation. Increased understanding into mechanisms of extracellular ATP metabolism by such ecto enzymes has also led to novel insights into the exquisite balance of nucleotide P2-receptor and adenosinergic P1-receptor signaling in those chronic hepatic diseases characterized by steatosis, fibrosis, and malignancy. This review will explore the developing role of purinergic signaling in the pathophysiology of liver disease and comment on potential future clinical applications.

Topics: Adenosine Triphosphate; Antigens, CD; Apyrase; Humans; Liver Diseases; Liver Regeneration; Liver Transplantation; Nucleotides; Receptors, Purinergic; Signal Transduction

A rapid radioassay was used to characterise the adenosine diphosphatase (ADPase) activities in human plasma. There was a major peak at pH 9.3, 80% of whose activity was attributable to non-specific alkaline phosphatase, with the remaining 20% probably due to a specific ADPase. There was also a small peak of ADPase activity at pH 4.0. Inhibitor and chromatographic studies showed that whilst much of this activity was attributable to non-specific acid phosphatase, there was a discrete acid ADPase. Assays of plasma ADPase activities in vascular disorders, including myocardial infarction, peripheral vascular disease and diabetes mellitus, reveal no alterations from control values. Activities of alkaline ADPase were elevated in both chronic and acute liver failure. Acid ADPase was also increased in chronic liver disease and it is suggested that alterations in ADPase activities in liver disorders may contribute to the haemostatic problems observed in these patients.

Topics: Acid Phosphatase; Acute Disease; Alkaline Phosphatase; Apyrase; Chromatography, Gel; Chronic Disease; Humans; Hydrogen-Ion Concentration; Kinetics; Liver Diseases; Myocardial Infarction; Phosphoric Monoester Hydrolases; Vascular Diseases