Regulation of norepinephrine transporter abundance by catecholamines and desipramine in vivo.

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Weinshenker D, White SS, Javors MA, Palmiter RD, Szot P

Regulation of norepinephrine transporter abundance by catecholamines and desipramine in vivo.

Brain Res. 2002 Aug 16;946(2):239-46.

PubMed ID

12137927 [ View in PubMed

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Abstract

The norepinephrine transporter (NET) regulates adrenoreceptor signaling by controlling the availability of synaptic norepinephrine (NE), and it is a direct target for some classes of antidepressant drugs. NET levels are normal in dopamine beta-hydroxylase knockout (Dbh -/-) mice that lack NE, demonstrating that the NET does not require endogenous NE for appropriate regulation under physiological conditions. In contrast, tyrosine hydroxylase knockout (Th -/-) mice that lack both NE and dopamine (DA) have reduced levels of NET, suggesting that it is down-regulated by a complete absence of catecholamines and not NE per se. Chronic treatment with the NET inhibitor, desipramine (DMI), reduced NET levels in both control and Dbh -/- mice, demonstrating that NE is not required for the regulation of NET by antidepressant drugs. There are some qualitative and quantitative differences in the down-regulation of the NET by catecholamine depletion and DMI treatment, suggesting that different mechanisms may be involved.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Desipramine	Sodium-dependent noradrenaline transporter	Protein	Humans	Yes	Inhibitor	Details