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Robert M Dores - One of the best experts on this subject based on the ideXlab platform.
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Evolution of gnathostome prodynorphin and proenkephalin: Characterization of a shark proenkephalin and prodynorphin cDNAs
General and comparative endocrinology, 2011Co-Authors: Leanne K. Komorowski, Stephanie Lecaude, Christian G. Westring, Phillip B. Danielson, Robert M DoresAbstract:Analyses of prodynorphin and proenkephalin cDNAs cloned from the central nervous system of the shark, Heterodontus portusjacksoni, provided additional evidence that these two opioid precursor-coding genes were most likely directly derived from a common ancestral gene. The two cDNAs could be aligned by inserting only seven gaps. The prodynorphin cDNA encodes five opioid sequences which could be aligned to opioid positions B through F in the proenkephalin cDNA. The sequence identity within the opioid positions was 59% at the amino acid level. Shark α-neo-endorphin, dynorphin A, and dynorphin B have amino acid motifs in common with shark met-enkephalin-8, and shark proenkephalin opioid positions E and F, respectively, which have not been observed in other gnathostome prodynorphin and proenkephalin precursor sequences. Shark prodynorphin encodes both kappa (α-neo-endorphin, dynorphin A, and dynorphin B) and delta (met-enkephalin and Leu-Enkephalin) opioid sequences. Mixed function prodynorphin precursors (encoding both enkephalins and dynorphins) are also found in representatives of the teleost fishes, lungfishes, and amphibians. It appears that only mammals evolved a prodynorphin precursor that exclusively encodes kappa opioid agonists (dynorphins).
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cloning of prodynorphin cdnas from the brain of australian and african lungfish implications for the evolution of the prodynorphin gene
Neuroendocrinology, 2004Co-Authors: Robert M Dores, Jean M.p. Joss, Stephanie Lecaude, Phillip B. Danielson, Cristina Sollars, Jenny Lee, Jasem Alrubaian, Isabelle Lihrman, Hubert VaudryAbstract:In mammals the opioids Met-enkephalin and Leu-Enkephalin are derived from a common precursor, proenkephalin, and as a result these neuropeptides are co-localized in enkephalinergic neurons. The mammal
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the phylogeny of met enkephalin and leu enkephalin studies on the holostean fish lepisosteus platyrhincus and the australian lungfish neoceratodus forsteri
General and Comparative Endocrinology, 1991Co-Authors: Lorraine K Mcdonald, Robert M Dores, Jean M.p. JossAbstract:Abstract Acid extracts of the brain of the holostean fish Lepisosteus platyrhincus and the forebrain of the dipnoan fish Neoceratodus forsteri were separately fractionated by Sephadex G-50 column chromatography. For both species, Met-enkephalin-related immunoreactivity was detected coeluting with the total volume internal standard. Higher-molecular-weight Met-enkephalin-containing immunoreactive peaks were not detected in these chromatographs. Furthermore, immunoreactive forms with antigenic determinants identical to mammalian dynorphin A(1–17), dynorphin A(1–8), α-neo-endorphin, or dynorphin B(1–13) were not detected in either species. Reverse-phase HPLC analysis of enkephalin-sized immunoreactive material indicated the presence of authentic Met-enkephalin and Leu-Enkephalin in the extracts of both species. In the brain of L. platyrhincus the molar ratio of Met-enkephalin to Leu-Enkephalin was approximately 3:1, whereas, the molar ratio of these enkephalins in the forebrain of N. forsteri was approximately 14:1. C-terminally extended forms of Met-enkephalin were also detected in the extracts of both species. These results suggest that the ancestral proenkephalin gene of both actinopterygian and sarcopterygian fish contained both the Met-enkephalin and Leu-Enkephalin sequences.
Hubert Vaudry - One of the best experts on this subject based on the ideXlab platform.
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cloning of prodynorphin cdnas from the brain of australian and african lungfish implications for the evolution of the prodynorphin gene
Neuroendocrinology, 2004Co-Authors: Robert M Dores, Jean M.p. Joss, Stephanie Lecaude, Phillip B. Danielson, Cristina Sollars, Jenny Lee, Jasem Alrubaian, Isabelle Lihrman, Hubert VaudryAbstract:In mammals the opioids Met-enkephalin and Leu-Enkephalin are derived from a common precursor, proenkephalin, and as a result these neuropeptides are co-localized in enkephalinergic neurons. The mammal
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immunocytochemical localization of enkephalins in the brain of the african lungfish protopterus annectens provides evidence for differential distribution of met enkephalin and leu enkephalin
The Journal of Comparative Neurology, 1998Co-Authors: Mauro Vallarino, Jeanlouis Thoumas, Maria Angela Masini, Michele Trabucchi, Nicolas Chartrel, Hubert VaudryAbstract:The distribution of various opioid peptides derived from proenkephalin A and B was studied in the brain of the African lungfish Protopterus annectens by using a series of antibodies directed against mammalian opioid peptides. The results show that both Met-enkephalin- and Leu-Enkephalin-immunoreactive peptides are present in the lungfish brain. In contrast, enkephalin forms similar to Met-enkephalin-Arg-Phe, or Met-enkephalin-Arg-Gly-Leu, as well as mammalian α-neoendorphin, dynorphin A (1–8), dynorphin A (1–13), or dynorphin A (1–17) were not detected. In all major subdivisions of the brain, the overwhelming majority of Met-enkephalin- and Leu-Enkephalin-immunoreactive cells were distinct. In particular, cell bodies reacting only with Leu-Enkephalin antibodies were detected in the medial subpallium of the telencephalon, the griseum centrale, the reticular formation, the nucleus of the solitary tract, and the visceral sensory area of the rhombencephalon. Cell bodies reacting only with Met-enkephalin antibodies were found in the lateral subpallium of the telencephalon, the caudal hypothalamus, and the tegmentum of the mesencephalon. The preoptic periventricular nucleus of the hypothalamus exhibited a high density of Met-enkephalin-immunoreactive neurons and only a few Leu-Enkephalin-immunoreactive neurons. The distribution of Met-enkephalin- and Leu-Enkephalin-immunoreactive cell bodies and fibers in the lungfish brain showed similarities to the distribution of proenkephalin A-derived peptides described previously in the brain of land vertebrates. The presence of Met-enkephalin- and Leu-Enkephalin-like peptides in distinct regions, together with the absence of dynorphin-related peptides, suggests that, in the lungfish, Met-enkephalin and Leu-Enkephalin may originate from distinct precursors. J. Comp. Neurol. 396:275–287, 1998. © 1998 Wiley-Liss, Inc.
Louis Gendron - One of the best experts on this subject based on the ideXlab platform.
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systematic replacement of amides by 1 4 disubstituted 1 2 3 triazoles in leu enkephalin and the impact on the delta opioid receptor activity
Bioorganic & Medicinal Chemistry Letters, 2013Co-Authors: Arnaud Proteaugagne, Kristina Rochon, Brigitte Guerin, Louis Gendron, Melissa Roy, Pierrejulien Albert, Yves L DoryAbstract:Abstract Using Cu(I)-catalyzed azide–alkyne cycloaddition in a mixed classical organic phase and solid phase peptide synthesis approach, we synthesized four analogs of Leu-Enkephalin to systematically replace amides by 1,4-disubstituted[1,2,3]triazoles. The peptidomimetics obtained were characterized by competitive binding, contractility assays and ERK1/2 phosphorylation. The present study reveals that the analog bearing a triazole between Phe and Leu retains some potency, more than all the others, suggesting that the hydrogen bond acceptor capacity of the last amide of Leu-Enkephalin is essential for the biological activity of the peptide.
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preparation and evaluation at the delta opioid receptor of a series of linear leu enkephalin analogues obtained by systematic replacement of the amides
ACS Chemical Neuroscience, 2013Co-Authors: Kristina Rochon, Arnaud Proteaugagne, Philippe Bourassa, Jeanfrancois Nadon, Jerome Cote, Veronique Bournival, Fernand Gobeil, Brigitte Guerin, Yves L Dory, Louis GendronAbstract:Leu-Enkephalin analogues, in which the amide bonds were sequentially and systematically replaced either by ester or N-methyl amide bonds, were prepared using classical organic chemistry as well as solid phase peptide synthesis (SPPS). The peptidomimetics were characterized using competition binding, ERK1/2 phosphorylation, receptor internalization, and contractility assays to evaluate their pharmacological profile over the delta opioid receptor (DOPr). The lipophilicity (LogD7.4) and plasma stability of the active analogues were also measured. Our results revealed that the last amide bond can be successfully replaced by either an ester or an N-methyl amide bond without significantly decreasing the biological activity of the corresponding analogues when compared to Leu-Enkephalin. The peptidomimetics with an N-methyl amide function between residues Phe and Leu were found to be more lipophilic and more stable than Leu-Enkephalin. Findings from the present study further revealed that the hydrogen-bond donor ...
Juan Carlos G. Marvizón - One of the best experts on this subject based on the ideXlab platform.
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enkephalins dynorphins and β endorphin in the rat dorsal horn an immunofluorescence colocalization study
The Journal of Comparative Neurology, 2009Co-Authors: Wenling Chen, Juan Carlos G. Marvizón, Niall P. MurphyAbstract:To characterize neuronal pathways that release opioid peptides in the rat dorsal horn, multiple-label immunohistochemistry, confocal microscopy, and computerized co-localization measures were used to characterize opioid-containing terminals and cells. An antibody that selectively recognized beta-endorphin labeled fibers and neurons in the ventral horn as well as fibers in the lateral funiculus and lamina X, but practically no fibers in the dorsal horn. An anti-enkephalin antibody, which recognized Leu-, Met-, and Phe-Arg-Met-enkephalin, labeled the dorsolateral funiculus and numerous puncta in laminae I-III and V of the dorsal horn. An antibody against Phe-Arg-Met-enkephalin, which did not recognize Leu- and Met-enkephalin, labeled the same puncta. Antibodies against dynorphin and prodynorphin labeled puncta and fibers in laminae I, II, and V, as well as some fibers in the rest of the dorsal horn. Dynorphin and prodynorphin immunoreactivities colocalized in some puncta and fibers, but the prodynorphin antibody additionally labeled cell bodies. There was no co-localization of dynorphin (or prodynorphin) with enkephalin (or Phe-Arg-Met-enkephalin). Enkephalin immunoreactivity did not colocalize with the C-fiber markers calcitonin gene-related peptide (CGRP), substance P, and isolectin B4. In contrast, there was some colocalization of dynorphin and prodynorphin with CGRP and substance P, but not with isolectin B4. Both enkephalin and dynorphin partly colocalized with vesicular glutamate transporter 2, a marker of glutamatergic terminals. The prodynorphin-positive neurons in the dorsal horn were distinct from neurons expressing mu-opioid receptors, neurokinin 1 receptors, and protein kinase C-gamma. These results show that enkephalins and dynorphins are present in different populations of dorsal horn neurons. In addition, dynorphin is present in some C-fibers.
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comparing analgesia and μ opioid receptor internalization produced by intrathecal enkephalin requirement for peptidase inhibition
Neuropharmacology, 2007Co-Authors: Wenling Chen, Bingbing Song, Lijun Lao, Orlando A Perez, Woojae Kim, Juan Carlos G. MarvizónAbstract:Opioid receptors in the spinal cord produce strong analgesia, but the mechanisms controlling their activation by endogenous opioids remain unclear. We have previously shown in spinal cord slices that peptidases preclude mu-opioid receptor (MOR) internalization by opioids. Our present goals were to investigate whether enkephalin-induced analgesia is also precluded by peptidases, and whether it is mediated by MORs or delta-opioid receptors (DORs). Tail-flick analgesia and MOR internalization were measured in rats injected intrathecally with Leu-Enkephalin and peptidase inhibitors. Without peptidase inhibitors, Leu-Enkephalin produced neither analgesia nor MOR internalization at doses up to 100 nmol, whereas with peptidase inhibitors it produced analgesia at 0.3 nmol and MOR internalization at 1 nmol. Leu-Enkephalin was 10 times more potent to produce analgesia than to produce MOR internalization, suggesting that DORs were involved. Selective MOR or DOR antagonists completely blocked the analgesia elicited by 0.3 nmol Leu-Enkephalin (a dose that produced little MOR internalization), indicating that it involved these two receptors, possibly by an additive or synergistic interaction. The selective MOR agonist endomorphin-2 produced analgesia even in the presence of a DOR antagonist, but at doses substantially higher than Leu-Enkephalin. Unlike Leu-Enkephalin, endomorphin-2 had the same potencies to induce analgesia and MOR internalization. We concluded that low doses of enkephalins produce analgesia by activating both MORs and DORs. Analgesia can also be produced exclusively by MORs at higher agonist doses. Since peptidases prevent the activation of spinal opioid receptors by enkephalins, the coincident release of opioids and endogenous peptidase inhibitors may be required for analgesia.
Kristina Rochon - One of the best experts on this subject based on the ideXlab platform.
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systematic replacement of amides by 1 4 disubstituted 1 2 3 triazoles in leu enkephalin and the impact on the delta opioid receptor activity
Bioorganic & Medicinal Chemistry Letters, 2013Co-Authors: Arnaud Proteaugagne, Kristina Rochon, Brigitte Guerin, Louis Gendron, Melissa Roy, Pierrejulien Albert, Yves L DoryAbstract:Abstract Using Cu(I)-catalyzed azide–alkyne cycloaddition in a mixed classical organic phase and solid phase peptide synthesis approach, we synthesized four analogs of Leu-Enkephalin to systematically replace amides by 1,4-disubstituted[1,2,3]triazoles. The peptidomimetics obtained were characterized by competitive binding, contractility assays and ERK1/2 phosphorylation. The present study reveals that the analog bearing a triazole between Phe and Leu retains some potency, more than all the others, suggesting that the hydrogen bond acceptor capacity of the last amide of Leu-Enkephalin is essential for the biological activity of the peptide.
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preparation and evaluation at the delta opioid receptor of a series of linear leu enkephalin analogues obtained by systematic replacement of the amides
ACS Chemical Neuroscience, 2013Co-Authors: Kristina Rochon, Arnaud Proteaugagne, Philippe Bourassa, Jeanfrancois Nadon, Jerome Cote, Veronique Bournival, Fernand Gobeil, Brigitte Guerin, Yves L Dory, Louis GendronAbstract:Leu-Enkephalin analogues, in which the amide bonds were sequentially and systematically replaced either by ester or N-methyl amide bonds, were prepared using classical organic chemistry as well as solid phase peptide synthesis (SPPS). The peptidomimetics were characterized using competition binding, ERK1/2 phosphorylation, receptor internalization, and contractility assays to evaluate their pharmacological profile over the delta opioid receptor (DOPr). The lipophilicity (LogD7.4) and plasma stability of the active analogues were also measured. Our results revealed that the last amide bond can be successfully replaced by either an ester or an N-methyl amide bond without significantly decreasing the biological activity of the corresponding analogues when compared to Leu-Enkephalin. The peptidomimetics with an N-methyl amide function between residues Phe and Leu were found to be more lipophilic and more stable than Leu-Enkephalin. Findings from the present study further revealed that the hydrogen-bond donor ...