Adenosine transport and metabolism in mouse leukemia cells and in canine thymocytes and peripheral blood leukocytes

Lum, Caliann T.; März, Richard; Plagemann, Peter G.W.; Wohlhueter, Robert M.

doi:10.1002/jcp.1041010202

Cited by 64 publications

(30 citation statements)

References 74 publications

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“…All of these findings indicate that in the presence of DCF, the major route of metabolism of adenosine during processing of whole blood is by pathways not affected in ADA-deficient blood, i.e. by rapid uptake into erythrocytes with phosphorylation (29,30) and subsequent metabolism of a proportion of the phosphorylated compounds to inosine and hypoxanthine via AMP deaminase, 5'-nucleotidase, and nucleoside phosphorylase. Additionally, we have found, in an ADA-deficient child in whom all erythrocytes had been replaced by ADA normal erythrocytes, that plasma adenosine concentration remained elevated at 1 and 2 ,uM.…”

Section: Resultsmentioning

confidence: 92%

Bone marrow transplantation only partially restores purine metabolites to normal in adenosine deaminase-deficient patients.

Hirschhorn¹,

Roegner-Maniscalco²,

Kuritsky³

et al. 1981

J. Clin. Invest.

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A B S T R A C T To delineate the extent to which bone marrow transplantation provides "enzyme replacement therapy", we have determined metabolite concentrations in two patients with adenosine deaminase (ADA) deficiency treated with bone marrow transplants and rendered immunologically normal. 10 yr after engraftment of lymphoid cells, erythrocyte deoxy ATP was markedly decreased compared to the marked elevations of deoxy ATP observed in untreated patients, but was still significantly elevated (62 and 90 vs. normal of6.0+6.0 nmol/ml packed erythrocytes). Similarly, deoxyadenosine and adenosine excretion were both markedly diminished compared to that of untreated patients but deoxyadenosine excretion was still clearly increased (20.1 and 38.6 vs. normal of <0.2 nmol/mg creatinine) while adenosine excretion was in the upper range of normal (7.0 and 8.1 vs. normal of 5.6+3.6 nmol/mg creatinine). Mononuclear cell deoxy ATP content was also elevated compared to normal (5.25 and 14.4 vs. 1.2+0.3). Separated mononuclear cells of bone marrow transplanted patients contain both donor lymphocytes and recipient monocytes. When mononuclear cells were depleted of the patients' own monocytes, the deoxy ATP content of the cells enriched for donor lymphocytes (i.e. monocyte depleted) was lower than that of the mixed mononuclear cells (2.2 vs. 5.26). Surprisingly, plasma adenosine was as high as in untreated ADA-deficient patients (3.2 and 1.5 vs. untreated of 0.3-3 ,uM). Consistent with the elevated plasma adenosine and Portions of this work were presented in part at the 92nd Annual Meeting ofthe Association ofAmerican Physicians and was published in abstract form in

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Section: Resultsmentioning

confidence: 92%

Bone marrow transplantation only partially restores purine metabolites to normal in adenosine deaminase-deficient patients.

Hirschhorn¹,

Roegner-Maniscalco²,

Kuritsky³

et al. 1981

J. Clin. Invest.

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“…The rats were injected intravenously with 0.2 ml of saline or dipyridamole (1 mg/kg body wt; Sigma Aldrich) 10 min before blood flow measurements with microspheres. Dipyridamole prevents the reuptake of released adenosine into cells by blocking the low Michaelis-Menten system for adenosine transport (32,41,48) and thereby induces a local accumulation of this substance, which is proportional to the released quantity.…”

Section: Methodsmentioning

confidence: 99%

Glucose-induced islet blood flow increase in rats: interaction between nervous and metabolic mediators

Carlsson

Olsson

Källskog

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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This study investigated the mechanisms for glucose-induced islet blood flow increase in rats. The effects of adenosine, adenosine receptor antagonists, and vagotomy on islet blood flow were evaluated with a microsphere technique. Vagotomy prevented the islet blood flow increase expected 3, 10, and 20 min after injection of glucose, whereas theophylline (a nonspecific adenosine receptor antagonist) prevented the islet blood flow increase from occurring 10 and 20 min after glucose administration. Administration of selective adenosine receptor antagonists suggested that the response to theophylline was mediated by A1receptors. Exogenous administration of adenosine did not affect islet blood flow, but local accumulation of adenosine, induced by the adenosine uptake inhibitor dipyridamole, caused a doubling of islet blood flow. In conclusion, the increased islet blood flow seen 3 min after induction of hyperglycemia is caused by the vagal nerve, whereas the increase in islet blood perfusion seen at 10 and 20 min after glucose administration is caused by both the vagal nerve and adenosine.

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“…3A, 4A) and over 90% of the intracellular radioactivity was associated with ATP (Table 3). We have demonstrated previously (Lum et al, 1979) that pretreatment of these cells with 20-30 pM dCF results to yield the final concentrations indicated. After 3 or 4 days of incubation at 3772, the cells were removed by incubation with trypsin-EDTA and enumerated in a Coulter counter.…”

Section: Isolation Of Variants Of Cho and Novikoff Cellsmentioning

confidence: 95%

Adenosine metabolism in wild‐type and enzyme‐deficient variants of Chinese hamster ovary and Novikoff rat hepatoma cells

Plagemann

Wohlhueter

1983

Journal Cellular Physiology

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Variants of Chinese hamster ovary and Novikoff rat hepatoma cells resistant to tubercidin and 2,5-diaminopurine, or to both drugs, were isolated, and their ability to convert adenosine and various adenosine analogs to nucleotides was compared to that of wild-type cells, both in intact cells and cell-free extracts. Adenosine deamination, and thus its conversion to nucleotides via inosine-hypoxanthine-inosine monophosphate, was inhibited by pretreatment of the cells or cell extracts with 2-deoxycoformycin. Cell-free extracts of the tubercidin-resistant variants, as well as of two adenosine-resistant mutants of Chinese hamster ovary cells, phosphorylated adenosine, tubercidin, pyrazofurin, or tricyclic nucleoside in the presence of ATP at less than 1% of the rate of extracts of wild-type cells. However, addition of phosphoribosyl pyrophosphate stimulated the conversion of adenosine to nucleotides 40-fold. Similarly, intact adenosine kinase-deficient cells failed to phosphorylate the adenosine analogs, but still converted adenosine to nucleotides at 5-10% the rate observed with wild-type cells. Phosphorylation of adenosine and tubercidin in wild-type cells was inhibited by substrate at concentration above 5-10 microM. In contrast, the rate of conversion of adenosine to nucleotides by adenosine kinase-deficient cells increased linearly up to a concentration of 400 microM adenosine, with the consequence that, at this concentration, these cells took up adenosine almost as rapidly as wild-type cells. Adenosine uptake by these kinase-deficient cells was inhibited by adenine and 5'-deoxyadenosine, and was largely abolished in mutants devoid also of adenine phosphoribosyltransferase. We conclude that adenosine is converted to nucleotides in adenosine kinase-deficient cells via adenine. Indirect evidence implicates 5'-methylthioadenosine phosphorylase as the enzyme responsible for the degradation of adenosine to adenine.

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Adenosine transport and metabolism in mouse leukemia cells and in canine thymocytes and peripheral blood leukocytes

Cited by 64 publications

References 74 publications

Bone marrow transplantation only partially restores purine metabolites to normal in adenosine deaminase-deficient patients.

Bone marrow transplantation only partially restores purine metabolites to normal in adenosine deaminase-deficient patients.

Glucose-induced islet blood flow increase in rats: interaction between nervous and metabolic mediators

Adenosine metabolism in wild‐type and enzyme‐deficient variants of Chinese hamster ovary and Novikoff rat hepatoma cells

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