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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Intrathecal infusion of the neuropeptide FF analogue, [D-Tyr1, (NMe)Phe3]neuropeptide FF (1DMe; 0.1 µm−0.1 mm) in anaesthetized rats produced a concentration-dependent decrease in the spinal outflow of dynorphin A (1–8)-like material, which persisted for at least 90 min after treatment with 10 µm−0.1 mm of the compound. Co-administration of d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; 1 µm) to block spinal µ-opioid receptors did not modify this effect, whereas naltrindole (10 µm) totally prevented it and nor-binaltorphimine (10 µm) reduced the post-effect. These data suggest that 1DMe triggers the release of endogenous opioids that stimulate mainly δ-opioid receptors, and secondarily κ-opioid receptors, thereby exerting a negative influence on dynorphin A (1–8)-like material outflow. Because dynorphin has pronociceptive properties, such a decrease in spinal dynorphin A (1–8)-like material release might underlie the long-lasting antinociceptive effects of intrathecally administered neuropeptide FF and analogues.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Recombinant herpes simplex virus-1 encoding the rat preproenkephalin A (HSVLatEnk1) was generated for driving the expression of preproenkephalin A-derived peptides in dorsal root ganglia of rats in vivo. Three weeks after infection via the hind footpads, quantitative RT-PCR and in situ hybridization experiments showed a strong expression of preproenkephalin A mRNA in lumbar dorsal root ganglia. In addition, a 40–160% increase in radioimmunoassayable Met-enkephalin-like material concentrations was found in the dorsal spinal cord and dorsal root ganglia, respectively, at the lumbar level in HSVLatEnk1-infected rats as compared with animals infected with β-galactosidase-encoding recombinant herpes simplex virus-1 or control rats. These data demonstrate the efficacy of the preproenkephalin A encoding vector and suggest that it should help in elucidating the role of Met-enkephalin-containing primary afferent fibers in pain transmission and/or control.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract : Because cholecystokinin (CCK) acts as a“functional” endogenous opioid antagonist, it has been proposedthat changes in central CCKergic neurotransmission might account for therelative resistance of neuropathic pain to the analgesic action of morphine.This hypothesis was addressed by measuring CCK-related parameters 2 weeksafter unilateral sciatic nerve section in rats. As expected, significantdecreases (-25-38%) in the tissue concentrations and in vitro release of bothsubstance P and calcitonin gene-related peptide were noted in the dorsalquadrant of the lumbar spinal cord on the lesioned side. In contrast, thetissue levels and in vitro release of CCK were unchanged in the same area inlesioned rats. Measurements in dorsal root ganglia at L4-L6 levels revealed nosignificant changes in proCCK mRNA after the lesion. However, sciatic nervesection was associated with a marked ipsilateral increase in both CCK-Breceptor mRNA levels in these ganglia (+70%) and the autoradiographic labelingof CCK-B receptors by [3H]pBC 264 (+160%) in the superficial layers of the lumbar dorsal horn. Up-regulation of CCK-B receptors rather than CCK synthesis and release probably contributes to increased spinal CCKergic neurotransmission in neuropathic pain.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 32 (1979), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The incubation of the 35,000 g supernatant of a rat brain stem homogenate in the presence of 7.5 mM-CaC12 for 10 min at 25°C resulted in a more than 2-fold increase in its tryptophan hydroxylase activity. This activation was irreversible and involved a reduction in the molecular weight of the enzyme, from 220,000 to 160,000. The partially proteolysed tryptophan hydroxylase, in contrast to the native enzyme, could not be activated by trypsin, sodium dodecyl sulphate, phosphatidylserine or phosphorylating conditions; dithiothreitol and Fe2+ were the only compounds whose stimulating effect on the enzymatic activity was not prevented by the Ca2+ -induced proteolysis of tryptophan hydroxylase.These findings suggest that the mol. wt. 60,000 fragment removed by the Ca2+ dependent neutral proteinase plays a critical role in the regulatory properties of tryptophan hydroxylase.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Striatal cholinergic interneurons play a crucial role in the control of movement as well as in motivational and learning aspects of behaviour. Neuropeptides regulate striatal cholinergic transmission and particularly activation of mu opioid receptor (MOR) inhibits acetylcholine (ACh) release in the dorsal striatum. In the present study we investigated whether this cholinergic transmission could be modulated by an enkephalin/MOR direct process. We show that mRNA and protein of MORs are expressed by cholinergic interneurons in the limbic/prefrontal territory but not by those in the sensorimotor territory of the dorsal striatum. These MORs are functional because potassium-evoked release of ACh from striatal synaptosomes was dose-dependently reduced by a selective MOR agonist, this effect being suppressed by a MOR antagonist. The MOR regulation of cholinergic interneurons presented a diurnal variation. (i) The percentage of cholinergic interneurons containing MORs that was 32% at the beginning of the light period (morning) increased to 80% in the afternoon. (ii) The MOR-mediated inhibition of synaptosomal ACh release was higher in the afternoon than in the morning. (iii) While preproenkephalin mRNA levels remained stable, enkephalin tissue content was the lowest (−32%) in the afternoon when the spontaneous (+35%) and the N-methyl-d-aspartate-evoked (+140%) releases of enkephalin (from microsuperfused slices) were the highest. Therefore, by acting on MORs present on cholinergic interneurons, endogenously released enkephalin reduces ACh release. This direct enkephalin/MOR regulation of cholinergic transmission that operates only in the limbic/prefrontal territory of the dorsal striatum might contribute to information processing in fronto-cortico-basal ganglia circuits.
    Type of Medium: Electronic Resource
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