Abstract
The specific interaction of platelets with ADP was discovered by Hellem and his co-workers at the University of Oslo [1] when they identified ADP as the compound present in an acidic extract of red blood cells that caused platelets to become trapped in a column of glass beads. The effect was specific for ADP, as neither AMP nor a range of naturally occurring nucleoside polyphosphates were active. Born [2] showed that aggregation of platelets could be studied quantitatively by a nephelometric technique and found that adenosine and 2-chloroadenosine [3] inhibit aggregation induced by ADP in a competitive manner. The initial conclusion that these nucleosides were competing with ADP for a specific receptor was revised in the light of several observations. The inhibitory effect of the nucleosides increases with time, and AMP is less active than adenosine. Furthermore, adenosine inhibits platelet aggregation induced by agents other than ADP (Fig. 18.1) [4), and in the case of nucleated thrombocytes of the frog, which aggregate when stimulated by thrombin but not with ADP, adenosine was still an inhibitor [5]. These discrepancies were resolved by the demonstration that adenosine increases the cyclic AMP content of platelets [6] and that it stimulates the adenylate cyclase activity of platelet membrane fragments [7]. Figure 18.2 shows that in platelets treated with different concentrations of adenosine either alone or in the presence of the cyclic AMP phosphodiesterase inhibitor, papaverine, there is a close correspondence between the increase in cyclic AMP level achieved and the degree of inhibition of aggregation observed.
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© 1983 Martinus Nijhoff Publishers, The Hague
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Mills, D.C.B., Macfarlane, D.E., Lemmex, B.W.G., Haslam, R.J. (1983). Receptors for Nucleosides and Nucleotides on Blood Platelets. In: Berne, R.M., Rall, T.W., Rubio, R. (eds) Regulatory Function of Adenosine. Developments in Pharmacology, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3909-0_18
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DOI: https://doi.org/10.1007/978-1-4613-3909-0_18
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