Disease relevance of adenosine

• Cellular injury and metabolic parameters were assessed after various interventions: Cells were preconditioned with anoxia (PC0), hypoxia (PC16), anoxic supernatant (SUP0), or hypoxic supernatant (SUP16) with or without the ADE receptor antagonist (SPT) or ADE deaminase (ADA) [1].
• In comparative growth rate experiments, wild type, nucleoside transport-deficient, and dCyd kinase-deficient CEM cells were equally sensitive to ddAdo toxicity, while, interestingly, a deficiency in Ado kinase correlated with a 5-fold decreased growth sensitivity to the purine ddN [2].

High impact information on adenosine

• Clinical trials of ADE administered during cardiac surgery are necessary to further define its beneficial effects in humans [1].
• The lethal effect was specific for adherent peritoneal cells (PC) (macrophages) and was prevented by exogenous addition of adenosine (Ado) or coformycin, a potent inhibitor of adenosine deaminase [3].
• We assume that 2-Cl Ado competes with intracellular Ado in macrophages and then causes the adenosine starvation resulting in the ATP decrease [3].
• Polymorphonuclear cells and lymphocytes to which 2-Cl Ado did not exhibit the lethal effect did not cause a significant ATP decrease of the cells [3].
• Kinetic and allosteric cooperativity in L-adenosine transport in chromaffin cells. A mnemonical transporter [4].

Biological context of adenosine

• Again,, a much lower level of enantioselectivity of deamination was observed than that of D- and L-adenosine [5].
• These results imply that Ado kinase may be an important factor in ddAdo phosphorylation by CEM cells [2].
• The effect of Ado and Homo on TNF-alpha cytotoxicity was at least partly mimicked by S-farnesylthioacetic acid, a selective inhibitor of the isoprenylcysteine carboxyl MTase, suggesting involvement of methylations of prenylated proteins in TNF-alpha-mediated cytotoxicity [6].
• Adenosine (A1) receptor activation prevented or reduced increases in [Ca]int and improved cell viability via a PKC and mito/sarcKATP channel-dependent mechanism [7].

Anatomical context of adenosine

• These studies show that, in lymphoblasts and myeloblasts, purine deoxyribonucleosides and their analogues are phosphorylated by dCyd kinase, Ado kinase, and dGuo kinase [8].
• L-Adenosine, L-5'-N-ethylcarboxamideadenosine, and methyl-N6-cyclohexyladenosine and 2'-5'-dideoxyadenosine (P site analog) were found to be ineffective in relaxing the bovine coronary arteries [9].
• In the present study, we used clonal smooth muscle DDT1 MF-2 cells that contain almost exclusively equilibrative inhibitor-sensitive (es) nucleoside transporters to test the hypothesis that L-adenosine is a permeant for these bidirectional nucleoside transporters [10].
• A mechanism which mediates the transport of the nonphysiological nucleoside, L-adenosine, was demonstrated in Plasmodium falciparum infected erythrocytes and naturally released merozoites [11].
• L-Adenosine was not a substrate for influx in freed intraerythrocytic parasites or in normal human erythrocytes nor was L-adenosine transported in a variety of cell types including other parasitic protozoa such as Crithidia luciliae, Trichomonas vaginalis, Giardia intestinalis, or the mammalian cells, Buffalo Green Monkey and HeLa cells [11].

Associations of adenosine with other chemical compounds

• In addition, an unusual metabolic property of parasitic adenosine deaminase was found in that L-adenosine was metabolised to L-inosine by both P. falciparum infected erythrocytes and merozoites, an activity which was inhibited by 50 nM deoxycoformycin [11].

Gene context of adenosine

• No other tested L-adenosine or L-guanosine analog was a substrate of dCK [12].
• L-Adenosine very weakly inhibited rat brain adenosine deaminase (ADA) activity with a Ki value of 385 microM [13].
• Even more important, the TNF-resistant L929 M1 tumors were rendered TNF-sensitive by the combined action of Ado and Homo. We conclude that Ado and Homo together enhance the effectiveness of TNF-alpha in vitro and in vivo, results that may have therapeutic implications [6].
• While the L-nucleoside analogues, L-adenosine, 2,6-diamino-9-(L-ribofuranosyl)purine and 4-amino-1-(L-ribofuranosyl)pyrazolo[3,4-d]-pyrimidine were selectively deaminated by P. falciparum ADA, L-thioinosine and L-thioguanosine were not [14].

References