[3H]GBR 12935 binding to human platelet membranes is sensitive to piperazine derivatives but not to dopamine uptake inhibitors

Life Sci. 1994;55(3):189-99. doi: 10.1016/0024-3205(94)00879-5.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Humans
  • Kinetics
  • Ligands
  • Male
  • Mazindol / pharmacology
  • Neurotransmitter Uptake Inhibitors / pharmacology*
  • Piperazines / metabolism*
  • Piperazines / pharmacology*
  • Rats

Substances

  • Antidepressive Agents
  • Ligands
  • Neurotransmitter Uptake Inhibitors
  • Piperazines
  • vanoxerine
  • 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine
  • Mazindol
  • Dopamine