Norepinephrine transporter knockout-induced up-regulation of brain alpha2A/C-adrenergic receptors
| Autor: | Michael Brüss, Marc G. Caron, Heinz Bönisch, Ralf Gilsbach, Marta Dziedzicka-Wasylewska, Agata Faron-Górecka, Zofia Rogóż |
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| Rok vydání: | 2006 |
| Předmět: |
Agonist
medicine.medical_specialty Adrenergic receptor medicine.drug_class Alpha (ethology) Biology Polymerase Chain Reaction Biochemistry Clonidine Mice Cellular and Molecular Neuroscience Norepinephrine Idazoxan Receptors Adrenergic alpha-2 Desipramine Internal medicine medicine Animals RNA Messenger Receptor Adrenergic alpha-Antagonists DNA Primers Mice Knockout Norepinephrine Plasma Membrane Transport Proteins Base Sequence Brain Endocrinology Norepinephrine transporter Catecholamine biology.protein medicine.drug |
| Zdroj: | Journal of Neurochemistry. 96:1111-1120 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/j.1471-4159.2005.03598.x |
| Popis: | The norepinephrine transporter (NET) is responsible for the rapid removal of norepinephrine released from sympathetic neurons; this release is controlled by inhibitory alpha(2)-adrenergic receptors (alpha(2)ARs). Long-term inhibition of the NET by antidepressants has been reported to change the density and function of pre- and postsynaptic ARs, which may contribute to the antidepressant effects of NET inhibitors such as desipramine. NET-deficient (NET-KO) mice have been described to behave like antidepressant-treated mice. By means of quantitative real-time PCR we show that mRNAs encoding the alpha(2A)-adrenergic receptor (alpha(2A)AR) and the alpha(2C)-adrenergic receptor (alpha(2C)AR) are up-regulated in the brainstem, and that alpha(2C)AR mRNA is also elevated in the hippocampus and striatum of NET-KO mice. These results were confirmed at the protein level by quantitative autoradiography. The NET-KO mice showed enhanced binding of the selective alpha(2)AR antagonist [(3)H]RX821002 in several brain regions. Most robust increases (20-25%) in alpha(2)AR expression were observed in the hippocampus and in the striatum. Significant increases (16%) were also seen in the extended amygdala and thalamic structures. In an 'in vivo' test, the alpha(2)AR agonist clonidine (0.1 mg/kg) caused a significantly greater reduction of locomotor activity in NET-KO mice than in wild-type mice, showing the relevance of our findings at the functional level. |
| Databáze: | OpenAIRE |
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