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  • 1
    Electronic Resource
    Electronic Resource
    Characterization of Two [3H]Ketanserin Recognition Sites in Rat Striatum (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 49 (1987), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Two [3H]ketanserin recognition sites are present in the rat striatum. The high-affinity site (Kd, 0.39 nM) is similar to the 5-hydroxytryptamine2 (5-HT2) site previously characterized by various investigators. The low-affinity site (Kd, 21.8 nM) has a unique pharmacologic specificity and is preferentially localized to rat striatum and septum. Conventional 5-HT2 antagonists as well as 5-HT and 5-HT uptake inhibitors are ineffective at inhibiting [3H]ketanserin binding to this low-affinity site. Also, chronic treatment with p-chlorophenylalanine, which depletes brain 5-HT, upregulates only the high-affinity site. Thus, in the striatum and septum, [3H]ketanserin labels a unique recognition site. This site has recently been shown to be associated with dopaminergic nerve endings and may regulate biogenic amine release.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1987.tb02444.x
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  • 2
    Electronic Resource
    Electronic Resource
    Coupling of Inositol Phospholipid Metabolism with Excitatory Amino Acid Recognition Sites in Rat Hippocampus (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 46 (1986), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Ibotenate, a rigid structural analogue of glutamate, markedly enhances the hydrolysis of membrane inositol phospholipids, as reflected by the stimulation of [3H]inositol monophosphate formation in rat hippocampal slices prelabeled with [3H]inositol and treated with Li+. Quisqualate, homocysteate, l-glutamate, and l-aspartate also induce a significant (albeit weaker) increase in [3H]inositol monophosphate formation, whereas N-methyl-d-aspartate, kainate, quinolinate, and N-acetylaspartylglutamate are inactive. The increase in [3H]inositol monophosphate formation elicited by the above-mentioned excitatory amino acids is potently and selectively antagonized by dl-2-amino-4-phosphonobutyric acid, a dicarboxylic amino acid receptor antagonist. These results suggest that, in the hippocampus, a class of dicarboxylic amino acid recognition sites is coupled with phospholipase C, the enzyme that catalyzes the hydrolysis of membrane inositol phospholipids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1986.tb12922.x
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Low nNOS protein in the locus coeruleus in major depression (2004)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 91 (2004), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Disruptions of glutamatergic and noradrenergic signaling have been postulated to occur in depressive disorders. Glutamate provides excitatory input to the noradrenergic locus coeruleus (LC). In this study, the location of immunoreactivity against neuronal nitric oxide synthase (nNOS), an intracellular mediator of glutamate receptor activation, was examined in the normal human LC, and potential changes in nNOS immunoreactivity that might occur in major depression were evaluated. Tissue containing LC, and a non-limbic, LC projection area (cerebellum) was obtained from 11 to 12 matched pairs of subjects with major depression and control subjects lacking major psychiatric diagnoses. In the LC region, nNOS immunoreactivity was found in large neuromelanin-containing neurons, small neurons lacking neuromelanin, and glial cells. Levels of nNOS immunoreactivity were significantly lower in the LC (− 44%, p 〈 0.05), but not in the cerebellum, when comparing depressed with control subjects. nNOS levels were positively correlated with brain pH values in depressed, but not control, subjects in both brain regions. Low levels of nNOS in the LC may reflect altered excitatory input to this nucleus in major depression. However, pH appears to effect preservation of nNOS immunoreactivity in subjects with depression. This factor may contribute, in part, to low levels of nNOS in depression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.2004.02792.x
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  • 4
    Electronic Resource
    Electronic Resource
    D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs (1995)
    Springer
    Psychopharmacology 120 (1995), S. 365-368 
    Details
    ISSN: 1432-2072
    Keywords: Antipsychotic drugs ; D4 dopamine receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The affinities of 13 atypical and 12 typical antipsychotic drugs for the cloned rat D4 dopamine receptor and the D4/D2 ratios were examined. Of the atypical antipsychotic drugs tested, only clozapine, risperidone, olanzapine, zotepine and tiospirone had affinities less than 20 nM. In fact, many atypical antipsychotic drugs had relatively low affinities for the cloned rat D4 receptor, with Ki values greater than 100 nM (Seroquel, fluperlapine, tenilapine, FG5803 and melperone). Additionally, several typical antipsychotic drugs had high affinities for the cloned rat D4 receptor, with Kis less than 20 nM (loxapine, chlorpromazine, fluphenazine, mesoridazine, thioridazine and trifluoroperazine). The ratios of D2/D4 affinities did not differentiate between these two types of antipsychotic drugs. Thus, D4 dopamine receptor affinity, used as a single measure, does not distinguish between the group of typical and atypical antipsychotic drugs analyzed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02311185
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  • 5
    Electronic Resource
    Electronic Resource
    Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2C receptor (1996)
    Springer
    Psychopharmacology 126 (1996), S. 234-240 
    Details
    ISSN: 1432-2072
    Keywords: Citalopram ; Fluoxetine ; Imipramine ; Antidepressants ; Serotonin 5-HT2C receptor ; Serotonin 5-HT2A receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interactions of the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine and its main metabolite norfluoxetine, and the tricyclic anti-depressant (TCA) imipramine with the rat serotonin 5-HT2C receptor in a clonal cell line and in the rat choroid plexus were investigated by radioligand binding and phosphoinositide (PI) hydrolysis assays. For comparison, the affinities of a variety of other antidepressants of different chemical classes for the cloned rat 5-HT2C and 5-HT2A receptors were also determined by radioligand binding assays. Fluoxetine displayed relatively high affinity for the 5-HT2C receptor in the choroid plexus, with a Ki value for inhibition of [3H]mesulergine binding of 55.4 nM. The Ki values for imipramine, norfluoxetine and citalopram were 136 nM, 203 nM, and 298 nM, respectively. Similar rank order of potency was detected in PI hydrolysis assays, which showed that these drugs are antagonists at the 5-HT2C receptor without exhibiting inverse agonist activity. [3H]Ketanserin (5-HT2A) binding assays revealed that the SSRIs fluoxetine, norfluoxetine and citalopram show 10- to 23-fold selectivity for the 5-HT2C receptor in vitro, whereas the TCA imipramine does not. Many other TCAs also had high to intermediate affinity for both 5-HT2A and 5-HT2C receptors. The present data provide evidence that fluoxetine, norfluoxetine and citalopram, along with many other antidepressant compounds, interact directly with the 5-HT2C receptor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246453
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