Astroglial dopamine transport is mediated by norepinephrine transporter.
The aim of this study was to clarify the characteristics of the dopamine (DA) transport mechanism in cultured rat cortical astrocytes. Reverse transcription-polymerase chain reaction (RT-PCR) with DA transporter (DAT)-, norepinephrine (NE) transporter (NET)- and organic cation transporter 3 (OCT3)-specific primers demonstrated that rat cortical astrocytes and frontal cortex expressed DAT, NET and OCT3 mRNA. Specific [(3)H]DA and [(3)H]NE uptake were each partly inhibited by 1 micro M decynium 22, an extraneuronal monoamine transporter (EMT) and OCT inhibitor. The selective NE uptake inhibitor nisoxetine (0.1 micro M) and the tricyclic antidepressant desipramine (1 micro M) very potently inhibited the specific uptake of both [(3)H]DA and [(3)H]NE in astrocytes. In contrast, 0.1 micro M GBR-12935, a selective and potent DA uptake inhibitor, had no inhibitory activity on the uptake of either compound. These results suggest that cortical astrocytes regulate extracellular DA and NE concentrations through the uptake of DA and NE by the glial NET but not by DAT. Furthermore, an uptake(2) mechanism contributes to DA uptake in cortical astrocytes.
Takeda
Hiroshi
H
Department of Pharmacology, and Intractable Diseases Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. ht0417@tokyo-med.ac.jp
Inazu
Masato
M
Matsumiya
Teruhiko
T
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D051381:Rats; D027981:Symporters / Q000378:metabolism*
D050484:Norepinephrine Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; D027981:Symporters; D004298:Dopamine; D009638:Norepinephrine