[3H]GBR 12935 binding to human platelet membranes is sensitive to piperazine derivatives but not to dopamine uptake inhibitors.
It remains controversial whether blood platelet can be used as a peripheral model for the central presynaptic dopaminergic neurons. We investigated the existence of dopamine transport complex in human blood platelet membranes using the selective dopamine uptake inhibitor [3H]GBR 12935 as a radioligand. In contrast to [3H]GBR 12935 binding to rat striatal dopamine carrier site, the high affinity [3H]GBR 12935 binding to platelet membranes was insensitive to mazindol and other dopamine uptake inhibitors. Piperazine derivatives including GBR 12909 were found to be potent inhibitors of [3H]GBR 12935 binding to platelet membranes. [3H]GBR 12935, piperazine derivative-sensitive binding to platelet membranes was inhibited by increasing sodium concentration. Kinetic experiments revealed that both association and dissociation rates of [3H]GBR 12935 binding were slower to platelet membranes than to striatal membranes. These results indicate that [3H]GBR 12935 binding to platelet membranes is different from the binding of this ligand to the dopamine uptake complex and seems to label a "piperazine acceptor" site which was previously demonstrated in brain and liver membranes.
Gordon
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I
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Weizman
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R
Rehavi
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M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008297:Male; D008454:Mazindol / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats
D000928:Antidepressive Agents; D008024:Ligands; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; C043425:vanoxerine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D008454:Mazindol; D004298:Dopamine