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• W2147612239 endingPage "9" @default.
• W2147612239 startingPage "951" @default.
• W2147612239 abstract "Certain antidepressant and psychostimulant drugs block the uptake of norepinephrine from the synaptic cleft by inhibiting norepinephrine transporter (NET) function. The effects of chronic occupation of the NET by these drugs on NET expression are poorly understood. We previously described down-regulation of the NET in cultured cells after continuous exposure to the tricyclic antidepressant desipramine. Here, the effects of structurally unrelated NET ligands, cocaine and amphetamine, on levels of NET and on NET function in HEK-293 cells transfected with human NET cDNA were investigated. All drug exposures were followed by incubation in drug-free media before harvesting and assays. Exposure of intact cells to cocaine for 3 days did not significantly affect the B(max) or K(D) of [(3)H]nisoxetine binding to NET in membrane homogenates, and did not alter levels of NET immunoreactivity or NET mRNA. In contrast, incubation of cells with amphetamine significantly reduced [(3)H]nisoxetine binding to NET and levels of NET immunoreactivity in a time-dependent manner, although levels of NET mRNA appeared to be unaffected. Exposures to cocaine or amphetamine resulted in significant reductions of [(3)H]norepinephrine uptake, although the magnitude of the reduction produced by amphetamine was much greater than cocaine. [(3)H]Nisoxetine binding to NET and NET protein levels were also reduced by exposure of cells to high concentrations of norepinephrine, although norepinephrine exposures were accompanied by changes indicative of cellular toxicity. Cocaine and amphetamine have distinctly different effects on NET expression after continuous exposure. The ability of only certain drugs to down-regulate the NET may provide clues to the unique therapeutic effects of antidepressants that are NET ligands." @default.
• W2147612239 created "2016-06-24" @default.
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• W2147612239 date "2000-12-01" @default.
• W2147612239 modified "2023-09-27" @default.
• W2147612239 title "Regulation of the human norepinephrine transporter by cocaine and amphetamine." @default.
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