Ecto-51-nucleotidase

Eckle T, Krahn T, Grenz A, Kohler D, Mittelbronn M, Ledent C, Jacobson MA, Osswald H, Thompson LF, Unertl K, Eltzschig HK (2007) Cardioprotection by ecto-5 -nucleotidase (CD73) and A2B adenosine receptors. Circulation 115(12) 1581—1590... 

Synnestvedt K, Furuta GT, Comerford KM, Louis N, Karhausen J, Eltzschig HK, Hansen KR, Thompson LF, Colgan SP (2002) Ecto-5 -nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J Clin Invest 110(7) 993-1002... 

Thompson LF, Eltzschig HK, Ibla JC, Van De Wiele CJ, Resta R, Morote-Garcia JC, Colgan SP (2004) Crucial role for ecto-5 -nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med 200(11) 1395-1405... 

The accumulation of adenosine in hypoxia is at least partially explained by hypoxia-mediated regulation of enzymes that are involved in adenosine metabolism (i) adenosine kinase (Decking et al. 1997) and (ii) 5 -nucleotidase (Headrick and Willis 1989 Kobayashi et al. 2000 Thompson et al. 2004). In particular, adenosine can be generated extracellularly through the hydrolysis of released nucleotides by ecto-5 -nucleotidases (Dunwiddie et al. 1997) or can be produced in the cytosol and transported to the extracellular space (Higgins et al. 1994). 

Fig. 4 Mechanisms involved in the extracellular inactivation of nucleotides (a, b and c) and adenosine (d) and their influence on purine concentration in the P2Y and PI receptor biophases, (a) NT-PDasel hydrolyses ATP and ADP very efficiently, thus preventing their action on P2Y receptors (b) NTPDase2 metabolizes ATP preferentially, allowing an accumulation of ADP and thus favouring activation of P2Yi, 12,13 receptors (c) NTPDase3 hydrolyses both ATP and ADP slowly, giving them time to activate both P2Y2,4 and P2Y 1,12,13 receptors. Formation of adenosine depends on the activity of ecto 5 -nucleotidase (CD73). Adenosine inactivation systems also influence adenosine concentration in the PI receptor biophase (d) the nucleoside transporters take up adenosine adenosine deaminase (ADA) regulates both the concentration of adenosine in the Ai receptor biophase and the functionality of Ai receptors.

Mihaylova-Todorova ST, Todorov LD, Westfall DP (2002) Enzyme kinetics and pharmacological characterization of nucleotidases released from the guinea pig isolated vas deferens during nerve stimulation evidence for a soluble ecto-nucleoside triphosphate diphosphohydrolase-like ATPase and a soluble ecto-5 nucleotidase-like AMPase. J Pharmacol Exp Ther 302 992-1001 Moos WH, Szotek DS, Bruns RF (1985) N6-Cycloal ky I adenosines. Potent Ai-selective adenosine agonists. J Med Chem 28 1383 4... 

Shinozaki, Y., Chujo, M., Mori, H., Inoue, M., Hori, M., Kamada,T. (1996). Role of activation of protein kinase C in the infard size-limiting effect of ischemic preconditioning through activation of ecto-5 -nucleotidase. Circulation 93, 781-791. 

Ecto-5 -nucleotidase (EC 3.1.3.5) has been identified on the outer surface of the ceU membrane and so its reaction product adenosine is released into the extracellular space. 

At regular intervals the immune status of the patient was assessed as well as the serum content and the urinary excretion of purine- and pyrimidine metabolites according to methods described in detail previously (6,8,10). The (deoxy)ribonucleotide content of the erythrocytes was analyzed by HPLC Ul)- Perchloric acid extracts of freshly withdrawn blood were made according to Cohen et al. (2) with minor modifications. In order to analyze deoxyribo-nucleotides the neutralized perchloric acid extracts were treated with sodium periodate according to Garret and Santi (12). 2,3 Di-phosphoglycerate (2,3-DPG) in the erythrocytes was determined as previously described (13). Ecto-5 -nucleotidase on intact lymphocytes was determined as described(14). Adenosine deaminase activity of the lymphocytes was determined essentially according to van Laar-hoven et al. (15). 

Circulating blood lymphocytes have relatively high activity of ecto 5 -nucleotidase (EC 3.1.3.5 - 5 N) as compared to monocytes of neutrophils (Webster et al 1978). This activity varies between different subpopulations B lymphocytes having about four times the activity of E rosetting T lymphocytes (Rowe et al 1980). 5 N activity also varies between T cell... 

L3rmphocyte Ecto-5 -nucleotidase deficiency in agammaglobulin-aemia, Science, 201 628-630. 

In our laboratory it was fotind that the specific activity of ecto-5 -nucleotidase decreased in neonatal mouse astroblast cultures when they were propagated through 10-20 passages (TRAMS LAUTER, unpublished data) ... 

Antibodies have been raised against 5 -nucleotidase of mouse liver plasma membranes by using purified membrane preparations from the same source (GURD EVANS, 1974) and the antiserum inhibited enzyme activity. Antisera raised against rat liver as well as rat fat cell plasma membranes inhibited ecto-5 -nucleotidase in isolated rat fat cells (NEWBY al., 1975). However, it is not known whether the immune-specific and the catalytic site of the enzyme are identical. 

Bachmann S, Le Hir M, Eckardt K-U. Co-localization of erythropoietin messenger RNA and ecto-5 -nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin. J Histochem C3dochem 1993 41 335-341. 

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