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

David Weinshenker, Sylvia S White, Martin A Javors, Richard D Palmiter, Patricia Szot

Howard Hughes Medical Institute, Box 357370, University of Washington, Seattle 98195, USA. dzw@genetics.washington.edu

Brain research 2002 Aug 16

filter terms:

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.

Citation

David Weinshenker, Sylvia S White, Martin A Javors, Richard D Palmiter, Patricia Szot. Regulation of norepinephrine transporter abundance by catecholamines and desipramine in vivo. Brain research. 2002 Aug 16;946(2):239-46