Extracellular levels of adenosine

Ballarin, M., Fredholm, B. B., Ambrosio, S. Mahy, N. (1991). Extracellular levels of adenosine and its metabolites in the striatum of awake rats inhibition of uptake and metabolism. Acta Physiol. Scand. 142 (1), 97-103. 

The extracellular levels of adenosine have been estimated to be approximately 30 to 500 nM, but may dramatically increase during hypoxia (Decking et al. 1997 MacLean et al. 1998 see Fredholm et al. 2001 Latini and Pedata 2001). Adenosine... 

Dipyridamole (Fig. 19.7) is an inhibitor of phosphodiesterase, which is responsible for the breakdown of cydic AMP. Inhibition of cAMP breakdown in some way inhibits the effect of ADP binding to platelets. In addition, dipyridamole inhibits the breakdown of adenosine to adenine thus the dmg raises extracellular levels of adenosine. Adenosine is an inhibitor of platelet a r ation. 

Yessotoxin also potentiated the calcium uptake induced in lymphocytes exposed to maitotoxin, although in this case, the effect was insensitive to SKF 96365 [48]. In the presence of extracellular calcium, but not in its absence, yessotoxin decreased cellular levels of adenosine 3, 5 -cyclic monophosphate, owing to activation of phosphodiesterases [38]. hi isolated mitochondria, yessotoxin opened the permeability transition pore, a voltage-dependent calcium channel, at concentrations between 10 and 10 M. Again, this effect required the presence of calcium in the incubation medium [49]. In the presence of the chemotactic tripeptide A-formyl-Meth-Leu-Phe, yessotoxin increased the motihty of mussel immunocytes, an effect that was again inhibited by verapamil [50]. 

To date, few detection methods are available for analysis of purine molecules in brain microdialysis samples. Most methods infuse purine molecules (retro-dialysis) directly to a brain region of interest then examine alterations in baseline levels of other neurotransmitters, such as DA [150]. When ATP or adenosine is detected in the brain using microdialysis, the dialysate samples are separated and detected by LC connected to either UV absorbance or fluorescence [72—76]. Striatal baseline levels of adenosine have been reported between 40 and 210 nM in the rat, while striatal ATP levels in the mouse are 60—170 nM using chemiluminescence [165]. What is most striking about extracellular adenosine and ATP measurements are the large basal ranges reported, which may be due to differences in LC methods, detector sensitivity, or the derivatiza-tion step required for fluorescence detection. 

Increased extracellular ATP breakdown has been seen in vitro during electrical field stimulation and during hypoxia (Lloyd et al., 1993). Although this source of extracellular adenosine accumulation remains a possibility, it has been found that inhibition of extracellular AMP hydrolysis does not significantly affect adenosine levels (Rosenberg et al., 2000). The main source of adenosine is thus probably intracellular, and possibly related to increased energy consumption. 

Okada M, Kawata Y, Kiryu K, Mizuno K, Wada K, Tasaki H, Kaneko S (1997) Effects of adenosine receptor subtypes on hippocampal extracellular serotonin level and serotonin reuptake activity. J Neurochem 69(6) 2581-2588... 

One of the major features of solid tumors and even small deposits of tumor tissue is deficiency in the level of oxygen, because of an inadequate vascular supply. The adenosine elevation in response to hypoxia is not exclusive to tumor tissues, but, in this context, the adenosine elevation is localized to the tumor microenvironment, since the surrounding tissue is normally oxygenated. Adenosine is generated mainly by two enzymatic systems intra- or extracellularly localized 5 -nucleoti-dases and cytoplasmic S-adenosylhomocysteine hydrolase. The processes of adenosine elimination in the cell involve reactions catalyzed by adenosine deaminase and adenosine kinase (Shryock and Belardinelli 1997) yielding inosine or 5 -AMP,... 

The levels of extracellular adenosine could increase step-wise up to micromolar levels as the outcome of the transport and/or diffusion of intracellular adenosine, formed from the large pools of intracellular ATP in hypoxic conditions (Sitkovsky et al. 2005,2008). Hypoxia can upregulate an adenine nucleotide-metabolizing ecto-enzyme cascade comprising ecto-ATP apyrase (CD39) and CD73 (Synnestvedt et al. 2002). 

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