Pharmacological characterization of dopamine transport in cultured rat astrocytes.
The effects of GBR-12909 (selective DA uptake inhibitor), zimelidine (selective 5-HT uptake inhibitor) and nisoxetine (selective NE uptake inhibitor) on the uptake of 30 nM [3H]DA into cultured rat astrocytes were examined. [3H]DA uptake was inhibited by approximately 50% by GBR-12909 or zimelidine in a concentration-dependent manner (100 nM to approximately 10 microM). Furthermore, the inhibition curves of GBR-12909 were biphasic, and uptake was completely inhibited by a high concentration of GBR-12909 (100 microM). [3H]DA uptake was also inhibited by approximately 50% by nisoxetine in a concentration-dependent manner (0.1 to approximately 100 nM), and nisoxetine was more potent than GBR-12909 or zimelidine. The inhibitory potencies were in the order nisoxetine > GBR-12909 > zimelidine. The uptake of [3H]DA under Na+-free conditions was approximately 50% of that under normal conditions. Thus, DA was taken up by both Na+-dependent and Na+-independent mechanisms. Nisoxetine (100 nM), zimelidine (100 microM) and GBR-12909 (10 microM) inhibited [3H]DA uptake into astrocytes only in the presence of Na+. On the other hand, this uptake was completely inhibited by a high concentration of GBR-12909 (100 microM) in the absence of Na+. The present data suggest that the Na+-dependent uptake of [3H]DA in cultured rat astrocytes may occur in the NE uptake system. Furthermore, astrocytes express the extraneuronal monoamine transporter (uptake2), which is an Na+-independent system, and this transporter is involved in the inactivation of centrally released DA.
Inazu
M
M
Department of Pharmacology, Tokyo Medical University, Japan.
Kubota
N
N
Takeda
H
H
Zhang
J
J
Kiuchi
Y
Y
Oguchi
K
K
Matsumiya
T
T
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D027981:Symporters; D015031:Zimeldine / Q000494:pharmacology
D002352:Carrier Proteins; D004298:Dopamine; D018765:Dopamine Uptake Inhibitors; D005473:Fluoxetine; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D012964:Sodium; D027981:Symporters; D015031:Zimeldine; C493226:Slc6a2 protein, rat; C011386:nisoxetine; C043425:vanoxerine