The dopamine agonism on ADP-stimulated platelets is mediated through D2-like but not D1-like dopamine receptors.
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 muM), dopamine in a range of 1 to 100 muM 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.
Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service of Baden-Württemberg-Hessen, Mannheim, Germany. a.schedel@iti-ma.blutspende.de
Angelika
A
Schedel
Patrick
P
Schloss
Harald
H
Klüter
Peter
P
Bugert
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D024141:Collagen Type IV / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008774:Methylphenidate / Q000494:pharmacology; D019007:P-Selectin / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D053657:Platelet-Rich Plasma / Q000187:drug effects / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D060149:Tetraspanin 30
D015703:Antigens, CD; D001552:Benzazepines; C554586:CD63 protein, human; D024141:Collagen Type IV; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; D019007:P-Selectin; D010880:Piperidines; D010980:Platelet Membrane Glycoproteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D060149:Tetraspanin 30; D008774:Methylphenidate; D020891:Raclopride; D000244:Adenosine Diphosphate; C104750:3-(4-(4-chlorophenyl-4-hydroxypiperidino)methyl)indole; D003024:Clozapine; D004298:Dopamine; D004837:Epinephrine