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      Extracellular adenine compounds, red blood cells and haemostasis: facts and hypotheses

      Blut
      Springer Nature

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          Abstract

          Previously, the role of adenine nucleotides was thought to be confined to the intracellular space of the cell. Research of the last decades has revealed that nucleotides also occur in the extracellular milieu. This survey deals with extracellular adenine compounds in the blood, focussing on their role as chemical mediators in the haemostatic effect of red cells. Erythrocytes may act as pro-aggregatory cells by at least two chemical mechanisms. Firstly, they can enhance platelet aggregation by releasing adenosine diphosphate (ADP), a well known platelet stimulatory substance. ADP is set free when red cells are stressed mechanically, for instance by shear forces generated in the blood stream; ample experimental evidence supporting this view is summarized. Secondly, erythrocytes efficiently take up extracellular adenosine via their nucleoside transporters, thereby removing a potent inhibitor of platelet function. Extracellular adenosine occurs in the blood stream, either directly released from various tissues or as the end product of extracellular adenine nucleotide metabolism, e.g. after degradation of red cell-born ADP or ATP. Finally, a novel mechanism of action of the antithrombotic drug dipyridamole, which has very recently been put forward, is demonstrated. Dipyridamole inhibits platelet function indirectly by blocking the uptake of extracellular adenosine via the nucleoside transporter of red cells; increased adenosine levels in turn are responsible for the antiaggregatory effect of dipyridamole.

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          Most cited references69

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          Aggregation of blood platelets by adenosine diphosphate and its reversal.

          G V Born (1962)
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            The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart.

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              The electronic aggregometer: a novel device for assessing platelet behavior in blood.

              A novel device for measuring platelet aggregation has been devised. The technique, which depends upon changes in electrical impedance caused by platelet accretion onto electrodes, is suitable for measurements of aggregation in either platelet-rich plasma (PRP) or blood. In PRP both turbidometric and electronic techniques give very similar responses to collagen, thrombin, prostaglandin endoperoxides, ADP, and arachidonic acid, although the electronic aggregometer gives no "shape-change" information and was somewhat more sensitive. In whole blood all these stimuli gave similar dose-related responses to those seen in PRP. The new technique is very suitable for investigating platelet pharmacology, since the inhibitors of aggregation, such as indomethacin and prostacyclin, can be conveniently quantitated in blood by using this technique.
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                Author and article information

                Journal
                Blut
                Blut
                Springer Nature
                0006-5242
                1432-0584
                October 1989
                October 1989
                : 59
                : 4
                : 367-374
                Article
                10.1007/BF00321207
                2676021
                0c71ee99-820f-4a87-a4a8-3533bea1c441
                © 1989
                History

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