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Thromb Haemost 1986; 55(01): 012-018
DOI: 10.1055/s-0038-1661437
Original Article
Schattauer GmbH Stuttgart

Mechanism of the Antiplatelet Action of Dipyridamole in Whole Blood: Modulation of Adenosine Concentration and Activity

Paolo Gresele
The Center for Thrombosis and vascular research department of medical research,University ofLeuven,Belgium
,
Jef Arnout
The Center for Thrombosis and vascular research department of medical research,University ofLeuven,Belgium
,
Hans Deckmyn
The Center for Thrombosis and vascular research department of medical research,University ofLeuven,Belgium
,
Jos Vermylen
The Center for Thrombosis and vascular research department of medical research,University ofLeuven,Belgium
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Publikationsverlauf

Received 16. Juli 1985

Accepted 04. Oktober 1985

Publikationsdatum:
19. Juli 2018 (online)

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Summary

Dipyridamole inhibits platelet aggregation in whole blood at lower concentrations than in plasma. The blood cells responsible for increased effectiveness in blood are the erythrocytes. Using the impedance aggregometer we have carried out a series of pharmacological studies in vitro to elucidate the mechanism of action of dipyridamole in whole blood. Adenosine deaminase, an enzyme breaking down adenosine, reverses the inhibitory action of dipyridamole. Two different adenosine receptor antagonists, 5’-deoxy-5’-methylthioadenosine and theophylline, also partially neutralize the activity of dipyridamole in blood. Enprofylline, a phosphodiesterase inhibitor with almost no adenosine receptor antagonistic properties, potentiates the inhibition of platelet aggregation by dipyridamole. An inhibitory effect similar to that of dipyridamole can be obtained combining a pure adenosine uptake inhibitor (RE 102 BS) with a pure phosphodiesterase inhibitor (MX-MB 82 or enprofylline). Mixing the blood during preincubation with dipyridamole increases the degree of inhibition. Lowering the haematocrit slightly reduces the effectiveness.

Although we did not carry out direct measurements of adenosine levels, the results of our pharmacological studies clearly show that dipyridamole inhibits platelet aggregation in whole blood by blocking the reuptake of adenosine formed from precursors released by red blood cells following microtrauma. Its slight phosphodiesterase inhibitory action potentiates the effects of adenosine on platelets.

Key words

Adenosine deaminase - Adenosine receptor antagonism - Impedance aggregometry - Phosphodiesterase inhibition - Platelet aggregation - Red blood cells
 

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