The dopamine transporter (DAT) is a protein regulating dopamine concentration in the synaptic cleft through the re-uptake mechanism. The DAT is the main target of psychostimulants and seems to play a pivotal role in neuronal degeneration and different neuropsychiatric disorders involving the dopamine system. Exhaustive research, however, regarding the presence of this protein in human platelets is still inconclusive, although it is thought that it might provide a peripheral tool to serve as a mean of exploring the same structure present in the brain. Therefore, we assessed some binding assays in platelets derived from healthy human subjects by means of 3H-WIN 35,428, a compound which is considered a selective ligand for the labelling of this protein, and by means of 125I-RTI-121, another compound with high specificity for DAT. The results showed that the binding of 3H-WIN-35,428 was too low to enable the detection of any structure; the binding of 125I-RTI-121, on the other hand, revealed the presence of two binding sites with pharmacological profiles similar to that of the serotonin transporter (SERT). In conclusions, therefore, platelets would not seem to be a useful model for exploring the DAT, given the prevalence therein of the SERT and the difficulty of labelling the DAT with the currently available ligands
Binding of H-WIN-35,428 and I-125-RTI-121 to human platelet membranes
BETTI, LAURA;GIANNACCINI, GINO;LUCACCHINI, ANTONIO;
2006-01-01
Abstract
The dopamine transporter (DAT) is a protein regulating dopamine concentration in the synaptic cleft through the re-uptake mechanism. The DAT is the main target of psychostimulants and seems to play a pivotal role in neuronal degeneration and different neuropsychiatric disorders involving the dopamine system. Exhaustive research, however, regarding the presence of this protein in human platelets is still inconclusive, although it is thought that it might provide a peripheral tool to serve as a mean of exploring the same structure present in the brain. Therefore, we assessed some binding assays in platelets derived from healthy human subjects by means of 3H-WIN 35,428, a compound which is considered a selective ligand for the labelling of this protein, and by means of 125I-RTI-121, another compound with high specificity for DAT. The results showed that the binding of 3H-WIN-35,428 was too low to enable the detection of any structure; the binding of 125I-RTI-121, on the other hand, revealed the presence of two binding sites with pharmacological profiles similar to that of the serotonin transporter (SERT). In conclusions, therefore, platelets would not seem to be a useful model for exploring the DAT, given the prevalence therein of the SERT and the difficulty of labelling the DAT with the currently available ligandsI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
