Characterization of the neuronal dopamine transporter DAT in human blood platelets.
Compelling evidence suggests a monoaminergic dysfunction in the aetiology of various neuro-psychiatric diseases such as depression, attention deficit hyperactivity disorder (ADHD), schizophrenia, addiction and Parkinson's disease. The efficiency of monoaminergic neurotransmission is controlled by rapid and efficient reuptake of dopamine out of the synaptic cleft by specific transporters for dopamine, serotonin and noradrenaline. In case of the serotonin transporter, many investigators have determined its function and expression also on peripheral cells such as blood platelets under the assumption that changes in protein expression in these cells might reflect neuronal changes. No comparable studies have so far been performed with respect to the dopamine transporter due to the lack of information about the existence of this protein in platelets. Here, we present pharmacological, immunological as well as microarray and PCR data that human blood platelets express the dopamine transporter protein (DAT), which is identical to that first identified in neurons. Because DAT expression is modulated also in non-neuronal cells independently of gene transcription, platelets may well serve as an easy accessible peripheral system to study DAT regulation in mental diseases or during drug treatment or drug abuse.
Department Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
Pascal
P
Frankhauser
Yvonne
Y
Grimmer
Peter
P
Bugert
Michael
M
Deuschle
Martin
M
Schmidt
Patrick
P
Schloss
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004298:Dopamine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000097:blood* / Q000235:genetics; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; D004298:Dopamine