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The dopamine agonism on ADP-stimulated platelets is mediated through D2-like but not D1-like dopamine receptors

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Abstract

Monoamines such as serotonin and epinephrine are known to be involved in platelet activation and aggregation. Dopamine is another monoamine identified in platelets, but published data about its effect on platelets and the receptors involved are controversial. In the present study, we investigated the dopamine agonism in platelets and the receptors involved in these pathways. Platelet-rich plasma (PRP) of healthy individuals was treated with agonists (ADP, epinephrine, dopamine) and various dopamine receptor and transporter antagonists such as SCH-23390, raclopride, clozapine, methylphenidate, and cocaine. Platelet activation was investigated by flow cytometry (CD62P and CD63 surface expression), optical aggregometry, and microaggregate adhesion to collagen IV in a flow chamber system. In our study, dopamine on its own had no effect on platelet activation in the different assays. However, when used in combination with ADP (10 μM), dopamine in a range of 1 to 100 μM significantly potentiated platelet microaggregate formation and adhesion to collagen under low shear flow conditions. Specific antagonists for D2-like receptors (L-741,626, raclopride, and clozapine) completely diminished the dopamine effect at selective concentrations, but not the effect of epinephrine. Neither the D1-like receptor antagonist SCH-23390 nor dopamine transporter antagonists (methylphenidate, cocaine) showed inhibitory effects on the dopamine agonism. Thus, dopamine is an ADP-dependent platelet agonist which acts via D2-like but not D1-like receptors or adrenergic receptors. Because many psychopharmacological drugs are directed to D2-like receptors, platelet dysfunction in patients being treated with such drugs may be linked to these mechanisms.

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Acknowledgements

We wish to thank Gabriele Rink for expert technical assistance and Daniela Griffiths for editorial assistance.

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Authors and Affiliations

  1. Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service of Baden-Württemberg-Hessen, Mannheim, Germany

    Angelika Schedel, Harald Klüter & Peter Bugert

  2. Biochemical Laboratory, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany

    Patrick Schloss

  3. Institut für Transfusionsmedizin und Immunologie, DRK-Blutspendedienst Baden-Württemberg – Hessen gGmbH, Friedrich-Ebert-Straße 107, 68167, Mannheim, Germany

    Angelika Schedel

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  1. Angelika Schedel
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  2. Patrick Schloss
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  3. Harald Klüter
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  4. Peter Bugert
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Correspondence to Angelika Schedel.

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Schedel, A., Schloss, P., Klüter, H. et al. The dopamine agonism on ADP-stimulated platelets is mediated through D2-like but not D1-like dopamine receptors. Naunyn-Schmied Arch Pharmacol 378, 431–439 (2008). https://doi.org/10.1007/s00210-008-0320-9

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  • DOI: https://doi.org/10.1007/s00210-008-0320-9

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