Adenosine as a metabolic regulator of tissue function: production of adenosine by cytoplasmic 5'-nucleotidases.

Abstract

Adenosine is a product of complete dephosphorylation of adenine nucleotides which takes place in various compartments of the cell. This nucleoside is a significant signal molecule engaged in regulation of physiology and modulation of the function of numerous cell types (i.e. neurons, platelets, neutrophils, mast cells and smooth muscle cells in bronchi and vasculature, myocytes etc.). As part a of purinergic signaling system, adenosine mediates neurotransmission, conduction, secretion, vasodilation, proliferation and cell death. Most of the effects of adenosine help to protect cells and tissues during stress conditions such as ischemia or anoxia. Adenosine receptors and nucleoside transporters are targets for potential drugs in many pathophysiological situations. The adenosine-producing system in vertebrates involves a cascade dephosphorylating ATP and ending with 5'-nucleotidase (EC 3.1.3.5) localized either on the membrane or inside the cell. In this paper the cytoplasmic variants of 5'-nucleotidase are broadly characterized as well as their clinical relevance. The role of AMP-selective 5'-nucleotidase (cN-I) in the heart, skeletal muscle and brain is highlighted. cN-I action is crucial during ischemia and important for the efficacy of some nucleoside-based drugs and in the regulation of the substrate pool for nucleic acids synthesis. Inhibitors used in studying the roles of cytoplasmic and membrane-bound 5'-nucleotidases are also described.

Neuroadaptations in Adenosine Receptor Signaling Following Long‐Term Ethanol Exposure and Withdrawal

“…Adenosine is continuously formed both intra‐ and extracellularly under stable cellular conditions (Fredholm et al., 2001). Intracellular adenosine is produced by dephosphorylation of adenosine monophosphate (AMP) by the 5′‐nucleotidase cN‐I (Borowiec et al., 2006; Schubert et al., 1979; Zimmermann et al., 1998) or by hydrolysis of S‐adenosyl‐homocysteine (Broch and Ueland, 1980; Turner et al., 2000). Adenosine is synthesized in the extracellular space by metabolism of adenine nucleotides (cAMP, AMP, ATP, ADP) by ectonucleotidases (Dunwiddie et al., 1997).…”

Dietary Supplementation of Ginger and Turmeric Rhizomes Modulates Platelets Ectonucleotidase and Adenosine Deaminase Activities in Normotensive and Hypertensive Rats

“…In the vascular system, these molecules can recruit and activate platelets, activate endothelial cells and induce vasoconstriction (Birk et al, ). As such, ADP at micromolar concentration is able to induce platelet aggregation in vivo while adenosine, produced by nucleotide catabolism, is recognized as a vasodilator and inhibitor of platelet aggregation that can decrease arterial blood pressure (Birk et al, ; Borowiec et al, ).…”

Evaluation and Characterization of the Effects of Ticagrelor on Serum and Urinary Uric Acid in Healthy Volunteers

“…31,32 Within cells, adenosine is either deaminated to inosine (subsequently metabolized to hypoxanthine) or converted to adenosine monophosphate, thereby becoming available for adenosine-5′-triphosphate synthesis; 33 the latter is the predominant pathway at physiological concentrations of adenosine. 34 Inhibition of erythrocyte nucleoside transporters would potentially increase extracellular/blood levels of adenosine, and this could lead to increased uric acid synthesis by tissues with high levels of xanthine oxidase, such as liver, kidney, and small intestine. 35 Evidence suggests that adenosine uptake in erythrocytes may be blocked by certain drugs, such as draflazine 36 and dipyridamole, 37 through inhibition of the nucleoside transporter.…”