[H-3] 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 [H-3] GBR 12935 as a radioligand. In contrast to [H-3] GBR 12935 binding to rat striatal dopamine carrier site, the high affinity [H-3] 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 [H-3] GBR 12935 binding to platelet membranes. [H-3] 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 [H-3] GBR 12935 binding were slower 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.