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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The mechanism by which two D3 receptor-preferring agonists, 7-hydroxydipropylaminotetralin (7-OH-DPAT) and quinelorane, modulate cocaine reinforcement was examined by monitoring nucleus accumbens dopamine levels with in vivo microdialysis while rats intravenously self-administered the following four different drug solutions consecutively: (1) cocaine; (2) a combination of cocaine plus a low dose of either agonist; (3) either agonist alone; and finally, (4) a physiological saline solution. Both 7-OH-DPAT (4 µg/infusion) and quinelorane (0.25 µg/infusion) decreased cocaine (0.25 mg/infusion) intake in a manner indicating an enhancement of cocaine reinforcement and simultaneously decreased the cocaine-induced elevations in nucleus accumbens dopamine levels by 〉50%. Subsequent self-administration of either 7-OH-DPAT (4 µg/infusion) or quinelorane (0.25 µg/infusion) alone resulted in significant, but stable, increases in drug intake, with a concurrent decrease in nucleus accumbens dopamine levels to ∼50% below nondrug baseline levels. These findings indicate that postsynaptic D3 receptor stimulation in the nucleus accumbens enhances the reinforcing properties of cocaine. In a second experiment, local application of 7-OH-DPAT via reverse dialysis (30 and 100 nM perfusate concentrations) dose-dependently decreased nucleus accumbens dopamine efflux to 76 ± 3.9 and 61 ± 6.3% of baseline, respectively, whereas there was no effect of this agonist on dopamine efflux in the ipsilateral striatum of these same animals. Coperfusion with the D3 receptor-preferring antagonist nafadotride dose-dependently blocked the effect of 7-OH-DPAT on nucleus accumbens dopamine efflux. These results suggest that, at low concentrations, 7-OH-DPAT selectively activates D3 receptors in vivo.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 35 (1980), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The properties of the histamine-forming enzyme in human brain samples were studied utilizing a radiochromatographic procedure. The influence of postmortem conditions was checked with rat brains, and the results indicated that the enzyme activity is not altered in situ for a delay not exceeding 4 h at ambient temperature. Moreover, tissue blocks or homogenates can be stored at low temperatures for up to 3 months with a good preservation of the enzyme activity. The data indicate that histamine synthesis in the human brain involves the „specific” histidine decarboxylase (HD, EC 4.1.1.22) and not the aromatic l-amino acid decarboxylase; (1) the optimum pH is 7.4 at 10-6m-l-histidine; (2) the apparent Km is about 3.10-5m; (3) it is inhibited by α-hydrazino histidine and brocresine but not affected by α-methyl DOPA. Moreover, a major portion of the enzyme is localized in a subcellular fraction containing nerve terminals and it shows an uneven regional distribution which parallels that observed in the brain of other mammalian species. Taken together these data strongly suggest that histamine could play a neurotransmitter role in the human brain.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The compound [3H-Tyr1,D-Ala2,Lcu-OH5]enkephalin has been synthesised as a potentially selective substrate for enkephalin dipeptidyl carboxypcptidase (enkephalinase) activity in brain. lncubations in the presence of homogenates and particulate fractions from rodent and human brain result in the formation of [3H]Tyr-D-Ala-Gly, which can be conveniently isolated by polystyrene bead column chromatography. The enzyme activity responsible for the hydrolysis of the Gly3-Phe4 amide bond of this substrate displays close resemblance to that hydrolysing the natural enkephalins at the same level. In addition, enkephalinase activity characterised in postmortem human brain is closely similar to that in rodent brain, with regard to optimal pH and apparent affinities of various substrates and inhibitors, including the potent compound thiorphan. Enkephalinase activity is distributed in a highly heterogeneous fashion among regions of human brain, the highest levels being found in globus pallidus and pars reticulata of the substantia nigra. This distribution is poorly correlated with that of opiate receptor binding sites but displays some resemblance to that of reported Met5-enkephalin levels.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 35 (1980), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: a-Fluoromethylhistidine (α-FMH), a new potent inhibitor of histidine decarboxylase (HD), has been used for in vitro and in vivo studies of brain HD. Following a preincubation with (+)-α-FMH, brain HD activity was inhibited in a time-dependent and concentration-dependent manner. The enzyme activity was not restored by overnight dialysis against standard buffer. The (–) antimer of α-FMH was ineffective. When injected intraperitoneally in a single dose of 20 mg/kg, (±)-α-FMH induced a complete loss in HD activity in cerebral cortex and hypothalamus as well as in peripheral tissues, such as stomach. At a dosage of 100 mg/kg (±)-α-FMH did not alter histamine-N-methyltransferase, DOPA decarboxylase, and glutamate decarboxylase activities. The maximal decrease of HD activity occurred after 2 h in both cerebral cortex and hypothalamus, but the time course of the recovery of enzyme activity was slower in the cerebral cortex. The enzyme activity reached control value within 3 days in hypothalamus and was not fully restored after 4 days in cerebral cortex. Contrasting with the diminished HD activity, a substantial concentration of histamine remained present in five regions of mouse brain. Thus, α-FMH is a highly specific irreversible inhibitor of brain HD activity and its efficacy makes it useful to study the physiological role of brain histamine.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 10 (1998), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: By screening an olfactory bulb cDNA library using dopamine receptor probes, we isolated the cDNA coding for the rat counterpart of an orphan receptor known as Edg-2, homologous to G protein-coupled receptors. In situ hybridization analysis showed that Edg-2 mRNA expression is restricted to myelinated structures, e.g. corpus callosum or peripheral nerves. A weaker expression in various peripheral organs was also detected in newborns. A 3.8-kb transcript was found at high levels in highly myelinated brain structures and sciatic nerve, and, at lower levels, in poorly myelinated peripheral organs, consistent with its occurrence in Schwann cells in the peripheral nervous system. One hundred percent of Edg-2 mRNA-containing cells in the brain also expressed mRNA encoding myelin-basic-protein, a marker of oligodendrocytes. This restricted olygodendrocytes localization was confirmed by the absence of cellular colocalization of Edg-2 and glial fibrillary acidic protein, an astrocytic marker. During prenatal development, Edg-2 mRNA expression was high in the cortical neuroepithelium and meningeal layer at E16, extended later to other neuroepithelia, and disappeared shortly after birth. During brain postnatal development, Edg-2 mRNA expression in myelinated structures followed a caudo-rostral gradient, similar to that of myelination. Thus, Edg-2 is the first G protein-coupled receptor found to be selectively expressed in myelin-forming cells in the nervous system and its temporal expression pattern is consistent with a dual role (i) in neurogenesis, during embryonic development, and (ii) in myelination and myelin maintenance, during postnatal life.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 43 (1984), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Marked reductions in opiate receptor binding (−42%), “enkephalinase” activity (−39%), and Met5-enkephalin levels (−72%) accompanied the well-established dopamine depletion in the substantia nigra pars compacta of Parkinsonian subjects. In contrast, enkephalinergic markers were not significantly modified in caudate nucleus.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 298 (1982), S. 373-375 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The addition of serotonin to slices from mouse cerebral cortex preincubated with 3H-glucose for 30 min, at a time when 3H-glycogen level in tissue has reached a plateau19, results in rapid hydrolysis of the 3H-polymer, The serotonin-induced gly-cogenolysis is concentration dependent, occurs with a ...
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 11 (1981), S. 144-146 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of (±)α-fluoromethylhistidine (α-FMH), a new histidine decarboxylase (HD) inhibitor, were investigated in vitro and in vivo. Following a preincubation with (±)α-FMH, brain HD-activity was progressively inhibited and could not be restored by dialysis, thus indicating the irreversible nature of this inhibition, Moreover, in vivo, a single intraperitoneal dose of 20 mg/kg of (±)α-FMH induced a complete and rapid loss of HD activity in gastric and brain tissues. The time-course of recovery was different according to the tissue studied. At a dose of 100mg/kg (±)α-FMH did not modify histamine-N-methyl transferase (HMT), DOPA decarboxylase and glutamate decarboxylase activities. A high affinity binding of3H-histamine was seen in particulate fractions from rat brains. The regional and subcellular distributions of these binding sites indicate that they are not related to HMT. They are likely to represent post-synaptic HA-receptors in view of their decrease after kainate-induced degeneration of neuronal perikarya in the striatum and their increase following interruption of the histaminergic inputs which suggested a denervation hypersensitivity. However, their pharmacological specificity was distinct from either H1-or H2-receptors, and the possibility of a modified conformational state of HA-receptors was raised by the selective effect of guanylnucleotides.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Thiorphan was designed to interact with critical residues of the active site of enkephalinase, as postulated on a hypothetical model (Fig. 1). The model was developed on the assumption that binding of enkephalins to this active site occurs in a manner analogous to that established at the molecular ...
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 287 (1980), S. 548-551 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The involvement of both HI- and H2-receptors in the cyclic AMP response to histamine in hippocampal slices was shown mainly by the biphasic rightward shift of concentration-response curves to this amine in the presence of low concentrations of mepyramine, a pure Hi-antihistamine and the additive ...
    Type of Medium: Electronic Resource
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