Objective To explore the possible differential trafficking properties of the dopamine D 1-like receptor subtypes, D 1 receptor and D5 receptor. Methods To visualize distributions of dopamine D 1-like receptor subtypes...Objective To explore the possible differential trafficking properties of the dopamine D 1-like receptor subtypes, D 1 receptor and D5 receptor. Methods To visualize distributions of dopamine D 1-like receptor subtypes at subcellular level, the yellow and cyan variants of green fluorescent protein （GFP） were used to tag D1 and D5 receptors. After transfection with the tagged dopamine receptors, the neuroblastoma cells NG108-15 were treated with D1 agonist SKF38393 or acetylcholine （ACh）. Then we observed the subcellular distributions of the tagged receptors under the confocal microscopy and tried to determine trafficking properties by comparing their distribution patterns before and after the drug treatment. Results In resting conditions, D 1 receptors located in the plasma membrane of NG108-15 cells, while D5 receptors located in both plasma membrane and cytosol. With the pre-treatment of SKF38393, the subcellular distribution of D1 receptors was changed. The yellow particle-like fluorescence of tagged D 1 receptors appeared in the cytosol, indicating that D 1 receptors were internalized into cytosol from the cell surface. Same situation also occurred in ACh pre-treatment. In contrast, the subcellular distribution of D5 receptors was not changed after SKF38393 or ACh treatment, indicating that D5R was not translocated to cell surface. Interestingly, when D1 and D5 receptors were co-expressed in the same cell, both kept their distinct subcellular distribution patterns and the trafficking properties. Conclusion Our present study reveals that in NG108-15 nerve cells, dopamine D1 and D5 receptors exhibit differential subcellular distribution patterns, and only D1 receptor has a marked trafficking response to the drug stimulation. We further discuss the potential role of the differential trafficking properties of D1-like receptors in complex modulation of DA signaling.展开更多
AIM:To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal syndrome.METHODS:The dopamine D_(1)receptor antagonist SCH23390 or the dopamine D_(2)receptor antagonist sulphide was adminis...AIM:To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal syndrome.METHODS:The dopamine D_(1)receptor antagonist SCH23390 or the dopamine D_(2)receptor antagonist sulphide was administered to rats chronically treated with either△^(9)-tetrahydrocannabinol(THC)or vehicle.Subjects were then injected with either SR141716A or vehicle and behavior was observed for 1 h.RESULTS:Administration of the cannabinoid receptor antagonist SR141716A to animals chronically treated with THC as described by Tsou et al(1995)produced a profound withdrawal syndrome.Treatment with dopamine antagonists did not attenuate cannabinoid precipitated withdrawal syndrome in THC tolerant animals while the agonists increased the syndrome.CONCLUSION:It is unlikely that the dopaminergic system plays a major role in mediating the behavioral aspects of the cannabinoid withdrawal syndrome.展开更多
文摘Objective To explore the possible differential trafficking properties of the dopamine D 1-like receptor subtypes, D 1 receptor and D5 receptor. Methods To visualize distributions of dopamine D 1-like receptor subtypes at subcellular level, the yellow and cyan variants of green fluorescent protein （GFP） were used to tag D1 and D5 receptors. After transfection with the tagged dopamine receptors, the neuroblastoma cells NG108-15 were treated with D1 agonist SKF38393 or acetylcholine （ACh）. Then we observed the subcellular distributions of the tagged receptors under the confocal microscopy and tried to determine trafficking properties by comparing their distribution patterns before and after the drug treatment. Results In resting conditions, D 1 receptors located in the plasma membrane of NG108-15 cells, while D5 receptors located in both plasma membrane and cytosol. With the pre-treatment of SKF38393, the subcellular distribution of D1 receptors was changed. The yellow particle-like fluorescence of tagged D 1 receptors appeared in the cytosol, indicating that D 1 receptors were internalized into cytosol from the cell surface. Same situation also occurred in ACh pre-treatment. In contrast, the subcellular distribution of D5 receptors was not changed after SKF38393 or ACh treatment, indicating that D5R was not translocated to cell surface. Interestingly, when D1 and D5 receptors were co-expressed in the same cell, both kept their distinct subcellular distribution patterns and the trafficking properties. Conclusion Our present study reveals that in NG108-15 nerve cells, dopamine D1 and D5 receptors exhibit differential subcellular distribution patterns, and only D1 receptor has a marked trafficking response to the drug stimulation. We further discuss the potential role of the differential trafficking properties of D1-like receptors in complex modulation of DA signaling.
文摘AIM:To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal syndrome.METHODS:The dopamine D_(1)receptor antagonist SCH23390 or the dopamine D_(2)receptor antagonist sulphide was administered to rats chronically treated with either△^(9)-tetrahydrocannabinol(THC)or vehicle.Subjects were then injected with either SR141716A or vehicle and behavior was observed for 1 h.RESULTS:Administration of the cannabinoid receptor antagonist SR141716A to animals chronically treated with THC as described by Tsou et al(1995)produced a profound withdrawal syndrome.Treatment with dopamine antagonists did not attenuate cannabinoid precipitated withdrawal syndrome in THC tolerant animals while the agonists increased the syndrome.CONCLUSION:It is unlikely that the dopaminergic system plays a major role in mediating the behavioral aspects of the cannabinoid withdrawal syndrome.
