[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.