The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
Lars Terenius - One of the best experts on this subject based on the ideXlab platform.
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CHARACTERIZATION OF IMMUNOREACTIVE DYNORPHIN B AND BETA -ENDORPHIN IN HUMAN PLASMA
Peptides, 1998Co-Authors: Jerzy Silberring, Lars Terenius, Ingrid NylanderAbstract:Dynorphins and beta-endorphin in human plasma were characterized and studied quantitatively using radioimmunoassay, high-performance liquid chromatography (HPLC), and mass spectrometry. Most immunoreactive (ir) dynorphin B and beta-endorphin in human plasma coeluted with authentic peptides in analysis. Dynorphin A was not detected. Added to human plasma it was rapidly converted into Leu-enkephalin-Arg6 followed by elimination of the C-terminal arginine after prolonged incubation. The rate of dynorphin A conversion was estimated at 40 pmol/min/microl plasma. This process was inhibited by the thiol protease inhibitor, PHMB and by EDTA. Dynorphin B, Alpha-Neoendorphin and big dynorphin were virtually not metabolized by plasma proteases under the same conditions. beta-endorphin was processed into beta-endorphin(1-19) and the corresponding C-terminal counterpart beta-endorphin(20-31) at a rate of about 25 pmol/min/microl of plasma. Based on the above data, a reliable strategy was established to measure dynorphin B- and beta-endorphin-ir in human plasma samples. The basal levels in a male control group were 0.99 +/- 0.11 (n = 11) and 16.3 +/- 1.5 (n = 11) fmol/ml plasma, respectively.
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Opiate modulation of dynorphin conversion in primary cultures of rat cerebral cortex.
Brain research, 1997Co-Authors: M Vlaskovska, Ingrid Nylander, S Hahne, L Kasakov, Jerzy Silberring, M. Schramm, Lars TereniusAbstract:Rat brain cortical cells in primary culture were used to investigate long-term effects of opiates on endopeptidases acting on dynorphin peptides. Enzyme activity in the soluble fraction of the cells converted dynorphin B to Leu-enkephalin-Arg6 and to a lesser extent to Leu-enkephalin. Five day treatment with 10 microM morphine increased the conversion to Leu-enkephalin-Arg6 by 370%. This effect was prevented by the presence of naloxone in the culture medium. The opiate-inducible activity was directed to the Arg-Arg bond in dynorphins with preference for dynorphin B > Alpha-Neoendorphin > > dynorphin A. The Km for the generation of Leu-enkephalin-Arg6 from dynorphin B was 40 microM. Enzyme activity was inhibited by dynorphin fragments, in the following order of potency: dynorphin A(1-13) > A(2-13) > A(1-17) > A(2-17) and by SH-reagents, suggesting the presence of a cysteine-protease. The opiate-stimulated dynorphin-converting enzyme (DCE)-activity affects the balance between dynorphin peptides (selective for kappa-opioid receptors) and enkephalin peptides (selective for delta-opioid receptors). Since both types of opioid peptides can influence the development of opiate tolerance, the change in the extent of this transformation may be functionally important.
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Differential metabolism of dynorphins in substantia nigra, striatum, and hippocampus.
Peptides, 1997Co-Authors: Johan Sandin, Ingrid Nylander, L Kasakov, Jerzy Silberring, Koichi Tan-no, Anders Winter, Lars TereniusAbstract:To map the proteolytic enzymes metabolizing dynorphins in brain structures, size-exclusion chromatography linked to electrospray ionization mass spectrometry was used. Enzymes extracted from rat hippocampus, striatum, and substantia nigra were tested for their capability of converting dynorphin-related peptides. Dynorphin A was the most resistant to proteolytic conversion, whereas Big dynorphin and dynorphin B-29 were slowly converted to dynorphin A and dynorphins A and B, respectively. Dynorphin B and Alpha-Neoendorphin were the least resistant. Dynorphin B was rapidly converted to Leu-enkephalin in the striatum and hippocampus but to Leu-enkephalin-Arg6 in the substantia nigra. Alpha-Neoendorphin was converted to Leu-enkephalin in all tissues investigated.
James H. Meador-woodruff - One of the best experts on this subject based on the ideXlab platform.
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Expression of prodynorphin-derived peptides and mRNA in guinea-pig cortex.
Neuropeptides, 1993Co-Authors: C. D. Ramsdell, James H. Meador-woodruffAbstract:The distributions and extent of processing of four prodynorphin-derived peptides (dynorphin A (1-17), dynorphin A (1-8), dynorphin B, and Alpha-Neoendorphin) were determined in ten regions of the cortex as well as in the striatum of the guinea-pig. There were significant differences between concentrations of these peptides in most cortical regions, with Alpha-Neoendorphin being several times more abundant than the other peptides, and dynorphin A (1-17) being present in the least amount. There were significant between-region differences in concentration for each peptide, although most regions had concentrations similar to those seen in the striatum. Concentrations of each peptide tended to be higher in piriform, entorhinal, motor, and auditory cortex than in other cortical regions. The extent of processing of prodynorphin varied across cortical regions as well, primarily due to the extent of processing to Alpha-Neoendorphin. Prodynorphin mRNA levels were not significantly different between cortical regions or from the amount observed in the striatum. Although specific regional variation exists, it appears that in general prodynorphin is expressed and processed in a similar manner in the cortex as in the striatum.
Gérard Tramu - One of the best experts on this subject based on the ideXlab platform.
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distribution of alpha neoendorphin immunoreactivity in the diencephalon and the brainstem of the dog
Journal of Chemical Neuroanatomy, 2002Co-Authors: P Pesini, R Pegoreigosa, Gérard Tramu, Rafael CoveñasAbstract:Abstract Alpha-Neoendorphin (α-NE) is an opiate decapeptide derived from the prodynorphin protein. Its anatomical distribution in the brain of mammals other than the rat, particularly in carnivores, is less well known than for other opiate peptides. In the present work, we have charted the distribution of α-NE immunoreactive fibers and perikarya in the diencephalon and the brainstem of the dog. The highest densities of labeled fibers were found in the substantia nigra and in patches within the nucleus of the solitary tract. Moderate densities appeared in the arcuate nucleus (Ar), median eminence, entopeduncular nucleus, ventral tegmental area, retrorubral area, periaqueductal central gray, interpeduncular nucleus and lateral parabrachial nucleus. Groups of numerous labeled perikarya were localized in the magnocellular hypothalamic nuclei, Ar and in the central superior and incertus nuclei in the metencephalon. Moreover, less densely packed fibers and cells appeared widely distributed throughout many nuclei in the region studied. These results are discussed with regard to the pattern described in other species. In addition, the present results were compared with the distribution of met-enkephalin immunoreactivity in the diencephalon and the brainstem of the dog that we have recently described. Although the distributions of these two peptides overlap in many areas, the existence of numerous differences suggest that they form separate opiate systems in the dog.
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Sexual Dimorphism in the Distribution of a-Neoendorphin-Like Immunoreactivity in the Anterior Pituitary of the Rat
Journal of neuroendocrinology, 1993Co-Authors: A. R. Bello, Olivier Kah, Dominique Croix, Philippe Ciofi, Gérard TramuAbstract:The localization of the opioid peptide Alpha-Neoendorphin (alpha-Neo-E) was studied in the anterior pituitary of normal and castrated male and normal female rats. Immunoreactive (ir) cells were noted in both sexes. These alpha-Neo-E-ir cells were further characterized using double immunostaining with an elution-restaining procedure. It was seen that in males, alpha-Neo-E-ir cells corresponded mainly to luteinizing hormone/follicle-stimulating hormone cells and a few thyroid-stimulating hormone (TSH) cells, whereas in females, virtually all alpha-Neo-E-ir cells corresponded to TSH cells. Castration of male rats caused, within 3 to 5 days a dramatic decrease in the number of alpha-Neo-E-ir gonadotrophs, whereas the number of alpha-Neo-E-ir TSH cells tended to increase. Two weeks after castration, however, most alpha-Neo-E-ir cells were also follicle-stimulating hormone-ir. This study demonstrates that in the anterior lobe of the rat, alpha-Neo-E-ir is located within gonadotrophs and/or thyrotrophs, depending on the sex. In addition, results obtained following castration suggest that the expression of this peptide in the anterior pituitary depends upon the steroid environment, possibly indicating that alpha-Neo-E is implicated in the regulation of the pituitary-gonadal axis.
Wen Fei Wang - One of the best experts on this subject based on the ideXlab platform.
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Human kappa opiate receptor second extracellular loop elevates dynorphin's affinity for human mu/kappa chimeras.
Journal of Biological Chemistry, 1994Co-Authors: Jia Bei Wang, Peter S. Johnson, Jun Min Wu, Wen Fei WangAbstract:Abstract To investigate roles of second extracellular loop sequences in peptide and nonpeptide ligand recognition by human opiate receptors, we have constructed a chimeric receptor in which this domain of the human mu opiate receptor has been replaced with that of the human kappa opiate receptor. The chimeric opiate receptor displays dramatically increased affinity for dynorphin peptides. Affinities for dynorphin A-(1-17), dynorphin A-(1-13), and Alpha-Neoendorphin increase by up to 250-fold when compared with the wild-type human mu opiate receptor. The chimera maintains recognition of the mu-selective ligands morphine and [D-Ala2,MePhe4,Gly-ol5]enkephalin and displays no significant changes in affinity for the kappa-selective small molecule ligand U50,488. The chimeric opiate receptor displays evidence for effective G-protein coupling; 100 nM dynorphin A-(1-17) is as effective as 100 nM morphine at inhibiting forskolin-stimulated adenyl cyclase activity through actions at the chimeric receptor. These data suggest that the putative second extracellular loop contributes substantially to the kappa receptor's selectivity in dynorphin ligand recognition.
Ingrid Nylander - One of the best experts on this subject based on the ideXlab platform.
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CHARACTERIZATION OF IMMUNOREACTIVE DYNORPHIN B AND BETA -ENDORPHIN IN HUMAN PLASMA
Peptides, 1998Co-Authors: Jerzy Silberring, Lars Terenius, Ingrid NylanderAbstract:Dynorphins and beta-endorphin in human plasma were characterized and studied quantitatively using radioimmunoassay, high-performance liquid chromatography (HPLC), and mass spectrometry. Most immunoreactive (ir) dynorphin B and beta-endorphin in human plasma coeluted with authentic peptides in analysis. Dynorphin A was not detected. Added to human plasma it was rapidly converted into Leu-enkephalin-Arg6 followed by elimination of the C-terminal arginine after prolonged incubation. The rate of dynorphin A conversion was estimated at 40 pmol/min/microl plasma. This process was inhibited by the thiol protease inhibitor, PHMB and by EDTA. Dynorphin B, Alpha-Neoendorphin and big dynorphin were virtually not metabolized by plasma proteases under the same conditions. beta-endorphin was processed into beta-endorphin(1-19) and the corresponding C-terminal counterpart beta-endorphin(20-31) at a rate of about 25 pmol/min/microl of plasma. Based on the above data, a reliable strategy was established to measure dynorphin B- and beta-endorphin-ir in human plasma samples. The basal levels in a male control group were 0.99 +/- 0.11 (n = 11) and 16.3 +/- 1.5 (n = 11) fmol/ml plasma, respectively.
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Opiate modulation of dynorphin conversion in primary cultures of rat cerebral cortex.
Brain research, 1997Co-Authors: M Vlaskovska, Ingrid Nylander, S Hahne, L Kasakov, Jerzy Silberring, M. Schramm, Lars TereniusAbstract:Rat brain cortical cells in primary culture were used to investigate long-term effects of opiates on endopeptidases acting on dynorphin peptides. Enzyme activity in the soluble fraction of the cells converted dynorphin B to Leu-enkephalin-Arg6 and to a lesser extent to Leu-enkephalin. Five day treatment with 10 microM morphine increased the conversion to Leu-enkephalin-Arg6 by 370%. This effect was prevented by the presence of naloxone in the culture medium. The opiate-inducible activity was directed to the Arg-Arg bond in dynorphins with preference for dynorphin B > Alpha-Neoendorphin > > dynorphin A. The Km for the generation of Leu-enkephalin-Arg6 from dynorphin B was 40 microM. Enzyme activity was inhibited by dynorphin fragments, in the following order of potency: dynorphin A(1-13) > A(2-13) > A(1-17) > A(2-17) and by SH-reagents, suggesting the presence of a cysteine-protease. The opiate-stimulated dynorphin-converting enzyme (DCE)-activity affects the balance between dynorphin peptides (selective for kappa-opioid receptors) and enkephalin peptides (selective for delta-opioid receptors). Since both types of opioid peptides can influence the development of opiate tolerance, the change in the extent of this transformation may be functionally important.
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Differential metabolism of dynorphins in substantia nigra, striatum, and hippocampus.
Peptides, 1997Co-Authors: Johan Sandin, Ingrid Nylander, L Kasakov, Jerzy Silberring, Koichi Tan-no, Anders Winter, Lars TereniusAbstract:To map the proteolytic enzymes metabolizing dynorphins in brain structures, size-exclusion chromatography linked to electrospray ionization mass spectrometry was used. Enzymes extracted from rat hippocampus, striatum, and substantia nigra were tested for their capability of converting dynorphin-related peptides. Dynorphin A was the most resistant to proteolytic conversion, whereas Big dynorphin and dynorphin B-29 were slowly converted to dynorphin A and dynorphins A and B, respectively. Dynorphin B and Alpha-Neoendorphin were the least resistant. Dynorphin B was rapidly converted to Leu-enkephalin in the striatum and hippocampus but to Leu-enkephalin-Arg6 in the substantia nigra. Alpha-Neoendorphin was converted to Leu-enkephalin in all tissues investigated.
