Adenosine formation extracellular adenosin

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.

Specific receptors are located on the cell membrane and binding of an extracellular messenger, e.g., a hormone, to these receptors activates the formation of an intraceUular messenger, a process that eventually results in the observed bioeffect. There is considerable evidence that adenosine is one of the extracellular messengers of neurosystems . In the central nervous system, for example, this compound inhibits activity and behaviorally has depressant effects The adenosine receptor seems to have a very specific steric requirement and, up to now, no polymeric purine derivative has been found effective in experiments in vivo however, the possibility of such applications has been demonstrated using isolated heart systems ... 

Schrader, J, Borst, M, Kelm, M, Smolenski, T, Deussen, A, Intra- and extracellular formation of adenosine by cardiac tissue. In Role of adenosine and adenine nucleotides in the biological system, (eds Imai, S and Nakazawa, M), Elsevier Science Publishers, Amsterdam, 1991,261-271. 

Nucleotidase (5 -N) is an integral glycoprotein of the cellular plasma membrane in a wide range of animal cells. Its functional role is still unclear. Possibilities. include recovery of purines and pyrimidines from the extracellular space, the extracellular formation of neuromodular adenosine from released nucleotidases and non-enzymatic functions related to the interaction of 5 -nucleotidase with compartments of the cytoskel-eton and extracellular matrix (Schoen et al., 1987). 5 -N catalyses the production of adenosine by the hydrolytic cleavage of 5 -nucleotide monophosphates (i.e. adenosine-5 -monophosphate). The development of 5 -N in the cerebellum was studied by Schoen et al. (1987, 1988, 1990). 

These observations provide convincing evidence that adenosine is continuously formed by the hepatocytes, and has to be rephos-phorylated in order to maintain the adenine nucleotide pool. The results depicted in Fig. 2 were only slightly modified when a mixture of AOPCP and p-glycerophosphate was added to the cell suspensions in order to inhibit the membranous 5 -nucleotidase and aspe-cific phosphatases. This rules out a significant participation of the former enzyme, as well as of the extracellular catabolism of adenine nucleotides released by dammaged hepatocytes, in the formation of adenosine. The production of adenosine thus most likely results from dephosphorylation of AMP inside the cells, by the cytoplasmic 5 -nucleotidase. From the observation that this formation of adenosine does not contribute to the physiological production of allantoin, it can be concluded that both the formation and utilization of adenosine proceed at the same rate in control conditions, and thus constitute a "futile cycle. From... 

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