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  • 1
    Electronic Resource
    Electronic Resource
    Regulation of striatal tyrosine hydroxylase phosphorylation by acute and chronic haloperidol (2004)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 20 (2004), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The typical neuroleptic haloperidol increases the state of phosphorylation and activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines. Here we show that the increases in TH phosphorylation produced by haloperidol at Ser31 and Ser40, two sites critically involved in the regulation of enzymatic activity, are abolished in dopamine D2 receptor-null mice and mimicked by the selective dopamine D2 receptor antagonist, eticlopride. Moreover, the ability of haloperidol and eticlopride to stimulate phosphorylation at both seryl residues is prevented by treatment with SL327, a compound that blocks activation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). We also show that chronic administration of haloperidol reduces the basal levels of phosphoSer31-TH and decreases the ability of the drug to stimulate Ser40 phosphorylation. These results provide a model accounting for the stimulation exerted by haloperidol on dopamine synthesis. According to this model, haloperidol increases TH activity via blockade of dopamine D2 receptors, disinhibition of dopaminergic projection neurons and ERK1/2-dependent phosphorylation of TH at Ser31 and Ser40. These studies also show that lower levels of phosphorylated TH are associated with chronic neuroleptic treatment and may be related to depressed dopaminergic transmission in nigrostriatal neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2004.03547.x
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  • 2
    Electronic Resource
    Electronic Resource
    Differences between brain structures in nuclear translocation and DNA binding of the glucocorticoid receptor during stress and the circadian cycle (2004)
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 19 (2004), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Glucocorticoid receptors (GRs) are transcription factors that, upon activation by glucocorticoids, translocate to the cell nucleus, and bind to specific response elements (GREs) in the promoter region of target genes. We analysed stress- and circadian-induced changes in nuclear translocation and GRE binding of GRs in the hippocampus and the prefrontal cortex of the rat brain. Nuclear translocation and binding to GRE were measured in nuclear extracts by Western blot and gel shift, respectively. When glucocorticoid levels were low, as during the light period of the circadian cycle, nuclear GRs and GRE binding were almost undetectable. However, the increase in glucocorticoid levels observed during the dark phase of the circadian cycle or after stress induced a massive nuclear translocation of GRs and GRE binding. These effects were corticosterone-dependent because they were suppressed by adrenalectomy and restored by the injection of corticosterone. Furthermore, GR translocation and GRE binding were of higher amplitude or lasted longer in the hippocampus than in the prefrontal cortex. By contrast, extracellular levels of glucocorticoids, measured by microdialysis in freely moving animals, were identical in the two structures. These results suggest that specific intracellular regulations of GR activity contribute to differentiate the effects of glucocorticoids in different regions of the brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2004.03267.x
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  • 3
    Electronic Resource
    Electronic Resource
    Absence of the dopamine D2 receptor leads to a decreased expression of GDNF and NT-4 mRNAs in restricted brain areas (1999)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 11 (1999), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Neurotrophic factors (NTFs) control the metabolic and electrophysiological properties of dopaminergic neurons in the brain. At the level of the substantia nigra, NTFs have been proposed to control dopamine release by regulating the firing rate of dopaminergic cells. This function is normally controlled by presynaptic dopaminergic autoreceptors. Dopamine has also been proposed to regulate the expression of NTFs and their receptors in the nigrostriatal pathway. Thus, an interaction between the signalling cascades activated by NTFs and dopamine receptors might possibly influence the physiology of dopaminergic neurons. Among dopamine receptors, D2 receptors (D2R) are the most abundant on dopaminergic neurons, where they exert autoreceptor functions. To test for an interaction between the NTF and dopaminergic pathways we have analysed the expression of NTFs and their receptors in D2R-deficient (D2R –/–) mice. Our study shows that the mRNA levels of brain-derived neurotrophic factor (BDNF), neurotrophin-3 and their corresponding receptors are not modified in the dopaminergic system of D2R –/– adult mice compared with wild-type littermates. However, a marked reduction of glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-4 (NT-4) mRNAs is observed in the striatum and parietal cortex of D2R –/– mice, respectively. These results implicate dopamine, acting through D2 receptors, in the local control of specific NTF expression. The down-regulation of GDNF and NT-4 expression might also contribute to the locomotor phenotype of D2R –/– mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.1999.00541.x
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  • 4
    Electronic Resource
    Electronic Resource
    Distinct functions of the two isoforms of dopamine D2 receptors (2000)
    [s.l.] : Macmillian Magazines Ltd.
    Nature 408 (2000), S. 199-203 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse. D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia. By a mechanism of ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/35041572
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  • 5
    Electronic Resource
    Electronic Resource
    Absence of opiate rewarding effects in mice lacking dopamine D2 receptors (1997)
    [s.l.] : Macmillan Magazines Ltd.
    Nature 388 (1997), S. 586-589 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Dopamine receptors have been implicated in the behavioural response to drugs of abuse. These responses are mediated particularly by the mesolimbic dopaminergic pathway arising in the ventral tegmental area and projecting to the limbic system. The rewarding properties of opiates and the somatic ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/388586a0
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  • 6
    Electronic Resource
    Electronic Resource
    Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors (1995)
    [s.l.] : Nature Publishing Group
    Nature 377 (1995), S. 424-428 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] A targeting vector was constructed to transfect embryonic stem (ES) cells that contained a dopamine D2 receptor (D2)FIG. 1 Disruption of the D2-receptor gene, a, D2-receptor knockout strategy. Top, the PGK-neo cassette was used to disrupt the ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/377424a0
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  • 7
    Electronic Resource
    Electronic Resource
    A chilled-out knockout (1998)
    [s.l.] : Nature America Inc.
    Nature genetics 19 (1998), S. 108-109 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Stress is the most common disorder of our century — most of us know too well what it means to be 'stressed out'. The word 'stress' is often used to mean anxiety regarding conditions that may be physical, environmental or emotional. In biological and molecular terms, however, stress is a ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/452
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  • 8
    Electronic Resource
    Electronic Resource
    Transgenic mice with inducible dwarfism (1989)
    [s.l.] : Nature Publishing Group
    Nature 339 (1989), S. 538-541 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] In rodents the pituitary gland is composed of the anterior, intermediate and posterior lobe, the former of which comprises five cell types: the somatotropes, lactotropes, thyrotropes, gonadotropes and corticotropes, distinguished by synthesis, release, and storage of a specific hormone. FIG. 1 ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/339538a0
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  • 9
    Electronic Resource
    Electronic Resource
    Adenovirus-2 E1A products repress enhancer-induced stimulation of transcription (1984)
    [s.l.] : Nature Publishing Group
    Nature 312 (1984), S. 608-612 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The adenovirus-2 early region 1A (E1A) products repress activation of transcription induced by the simian virus 40, polyoma virus and adenovirus-2 E1A enhancers. The repression probably involves an interaction between the enhancer elements and a trans-acting factor(s), possibly the E1A products ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/312608a0
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