Abstract
Methamphetamine (METH) causes release of stored intracellular dopamine (DA). We explored the interactions of METH with the recombinant human vesicular monoamine (hVMAT2) and/or human DA transporters (hDAT) in transfected mammalian (HEK293) cells and compared the findings with those for DA. In 'static' release assays at 37°C, less than 20% of pre-loaded [3H]DA was lost after 60 min, while nearly 80% of pre-loaded [3H]METH was lost at 37°C under non-stimulated conditions. Results obtained by measuring substrate release using a superfusion apparatus revealed an even greater difference in substrate efflux. At pH 7.4, nearly all of the pre-loaded [3H]METH was lost after just 6 min, compared with the loss of 70-80% of pre-loaded [ 3H]DA (depending on cell type) after superfusion for 32 min. Increasing the extracellular pH from 7.4 to 8.6 had opposite effects on [ 3H]DA and [3H]METH retention. At pH 8.6, [ 3H]METH was retained more effectively by both hDAT and hDAT-hVMAT2 cells, compared with results obtained at extracellular pH 7.4. [ 3H]DA, however, was more effectively retained at pH 7.4 than at pH 8.6. These data suggest that DA and METH interact differently with the DAT and VMAT2, and require different H+ concentrations to exert their effects.
Original language | English (US) |
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Pages (from-to) | 1149-1159 |
Number of pages | 11 |
Journal | Journal of neurochemistry |
Volume | 96 |
Issue number | 4 |
DOIs | |
State | Published - Feb 2006 |
Keywords
- Dopamine
- Dopamine transporter
- Methamphetamine
- Release
- Vesicular transporter
- pH
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience