It was recently proposed that the human platelet might serve as a pharmacologic model for the study of central nervous system dopaminergic neurons in patients with diseases such as parkinsonism, Huntington's chorea, and schizophrenia. To investigate this proposal, the characteristics of dopamine accumulation by human platelets were determined and compared to those of dopamine accumulation by central nervous system dopaminergic neurons as well as by isolated platelet amine storage granules. The accumulation of dopamine by human platelets was not kinetically saturable, and was not significantly inhibited by ouabain, metabolic inhibitors, or tricyclic antidepressant drugs. Serotonin did not compete for the accumulation of dopamine by platelets, but reserpine, tetrabenazine, and N-ethylmaleimide each inhibited platelet dopamine accumulation. The accumulation of dopamine by isolated platelet amine storage granules was similarly not saturable, was not diminished by ouabain, metabolic inhibitors, or tricyclic antidepressants, yet was inhibited by reserpine, tetrabenazine, or N-ethylmaleimide. The accumulation of dopamine by human platelets does not meet the requirements of a model for the high-affinity, kinetically saturable uptake of dopamine by central nervous system dopaminergic neurons which is inhibited by ouabain and metabolic inhibitors. The data suggest that dopamine accumulation by human platelets is mediated via passive diffusion of dopamine into the platelet followed by binding of dopamine by the amine storage granules. These findings have relevance to studies of platelet dopamine uptake in parkinsonism and Huntington's chorea.
ASJC Scopus subject areas
- Developmental Neuroscience