Pharmacological characterization of dopamine transport in cultured rat astrocytes

The effects of GBR-12909 (selective DA uptake inhibitor), zimelidine (selec tive 5-HT uptake inhibitor) and nisoxetine (selective NE uptake inhibitor) on the uptake of 30 nM [H-3]DA into cultured rat astrocytes were examined. [H-3]DA uptake was inhibited by approximately 50 % by GBR-12909 or zimelidi ne in a concentration-dependent manner (100 nM similar to 10 mu M). Further more, the inhibition curves of GBR-12909 were biphasic, and uptake was comp letely inhibited by a high concentration of GBR-12909 (100 mu M). [H-3]DA u ptake was also inhibited by approximately 50 % by nisoxetine in a concentra tion-dependent manner (0.1 similar to 100 nM), and nisoxetine was more pote nt than GBR-12909 or zimelidine. The inhibitory potencies were in the order nisoxetine > GBR-12909 > zimelidine. The uptake of [H-3]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. Nisoxet ine (100 nM), zimelidine (100 mu M) and GBR-12909 (10 mu M) inhibited [H-3] DA uptake into astrocytes only in the presence of Na+. On the other hand, t his uptake was completely inhibited by a high concentration of GBR-12909 (1 00 mu M) in the absence of Na+. The present data suggest that the Na+-depen dent uptake of [H-3]DA in cultured rat astrocytes may occur in the NE uptak e system. Furthermore, astrocytes express the extraneuronal monoamine trans porter (uptake(2)), which is an Na+-independent system, and this transporte r is involved in the inactivation of centrally released DA.