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Opioid Receptors and Endorphinergic Systems

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (28 June 2019) | Viewed by 10583

Special Issue Editor

Special Issue Information

Dear Colleagues,

Different cell populations express selected types of opioid receptors (i.e., m, d and k), being not only a target, but even a source for a number of biologically active end-products of endorphin genes, including for example the prodynorphin and the pro-enkephalin genes. The interaction between these peptides and their related receptors plays a crucial role in signal transduction circuitries. It is now increasingly becoming evident that the activity of endorphinergic systems is fashioned at multiple interconnected levels and it is controlled by a complex interplay between cell signaling, nucleosomal assembly, the establishment of multifaceted transcriptional motifs and the temporal and spatial organization of chromatin into loops and domains. Opioid peptides not only elicit paracrine and autocrine mechanisms of cell regulation, but they have also been found to act intracellularly. It turns out that cell nuclei harbor the potential for intrinsic signal transduction pathway(s). The term intracrine has been proposed for growth regulatory peptides that have been shown to act within their cell of synthesis at the level of the nuclear envelope, chromatin, or other subnuclear components. Consistent evidence links known intracrines with transcriptional responses and self-sustaining loops that behave as long-lived signals imparting features characteristic of cell growth, differentiation and memory. Within this context, we have shown that the prodynorphin gene and its biologically active product dynorphin B act as major conductors of cardiogenesis in both embryonic and adult stem cells, and that dynorphin B can act in an intracrine fashion at the level of nuclear opioid receptors in stem cells, coupling nuclear signaling with the transcription of cardiogenic genes.

This Special Issue is focused on novel, emerging paradigms from the study (original research articles or reviews) of opioid receptors, and opioid peptides. Particular emphasis will be addressed in unraveling their paracrine, autocrine and intracrine patterning in the modulation of cell signaling networks and fate decisions, at the level of both somatic and stem cells of different origin.

Prof. Dr. Carlo Ventura
Guest Editor

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Keywords

  • Opioid receptors
  • Opioid peptides
  • Autocrine
  • Paracrine
  • Intracrine regulation
  • Cell signaling
  • Gene expression
  • Differentiation
  • Growth regulation
  • Somatic cells
  • Stem cells

Published Papers (3 papers)

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Research

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21 pages, 5016 KiB  
Article
Mutual Enhancement of Opioid and Adrenergic Receptors by Combinations of Opioids and Adrenergic Ligands Is Reflected in Molecular Complementarity of Ligands: Drug Development Possibilities
by Robert Root-Bernstein, Beth Churchill, Miah Turke, Udaya K. Tiruttani Subhramanyam and Joerg Labahn
Int. J. Mol. Sci. 2019, 20(17), 4137; https://doi.org/10.3390/ijms20174137 - 24 Aug 2019
Cited by 9 | Viewed by 4180
Abstract
Crosstalk between opioid and adrenergic receptors is well characterized and due to interactions between second messenger systems, formation of receptor heterodimers, and extracellular allosteric binding regions. Both classes of receptors bind both sets of ligands. We propose here that receptor crosstalk may be [...] Read more.
Crosstalk between opioid and adrenergic receptors is well characterized and due to interactions between second messenger systems, formation of receptor heterodimers, and extracellular allosteric binding regions. Both classes of receptors bind both sets of ligands. We propose here that receptor crosstalk may be mirrored in ligand complementarity. We demonstrate that opioids bind to adrenergic compounds with micromolar affinities. Additionally, adrenergic compounds bind with micromolar affinities to extracellular loops of opioid receptors while opioids bind to extracellular loops of adrenergic receptors. Thus, each compound type can bind to the complementary receptor, enhancing the activity of the other compound type through an allosteric mechanism. Screening for ligand complementarity may permit the identification of other mutually-enhancing sets of compounds as well as the design of novel combination drugs or tethered compounds with improved duration and specificity of action. Full article
(This article belongs to the Special Issue Opioid Receptors and Endorphinergic Systems)
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Review

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22 pages, 1710 KiB  
Review
Intracrine Endorphinergic Systems in Modulation of Myocardial Differentiation
by Silvia Canaider, Federica Facchin, Riccardo Tassinari, Claudia Cavallini, Elena Olivi, Valentina Taglioli, Chiara Zannini, Eva Bianconi, Margherita Maioli and Carlo Ventura
Int. J. Mol. Sci. 2019, 20(20), 5175; https://doi.org/10.3390/ijms20205175 - 18 Oct 2019
Cited by 2 | Viewed by 2754
Abstract
A wide variety of peptides not only interact with the cell surface, but govern complex signaling from inside the cell. This has been referred to as an “intracrine” action, and the orchestrating molecules as “intracrines”. Here, we review the intracrine action of dynorphin [...] Read more.
A wide variety of peptides not only interact with the cell surface, but govern complex signaling from inside the cell. This has been referred to as an “intracrine” action, and the orchestrating molecules as “intracrines”. Here, we review the intracrine action of dynorphin B, a bioactive end-product of the prodynorphin gene, on nuclear opioid receptors and nuclear protein kinase C signaling to stimulate the transcription of a gene program of cardiogenesis. The ability of intracrine dynorphin B to prime the transcription of its own coding gene in isolated nuclei is discussed as a feed-forward loop of gene expression amplification and synchronization. We describe the role of hyaluronan mixed esters of butyric and retinoic acids as synthetic intracrines, controlling prodynorphin gene expression, cardiogenesis, and cardiac repair. We also discuss the increase in prodynorphin gene transcription and intracellular dynorphin B afforded by electromagnetic fields in stem cells, as a mechanism of cardiogenic signaling and enhancement in the yield of stem cell-derived cardiomyocytes. We underline the possibility of using the diffusive features of physical energies to modulate intracrinergic systems without the needs of viral vector-mediated gene transfer technologies, and prompt the exploration of this hypothesis in the near future. Full article
(This article belongs to the Special Issue Opioid Receptors and Endorphinergic Systems)
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15 pages, 1454 KiB  
Review
Interplay between the Endogenous Opioid System and Proteasome Complex: Beyond Signaling
by Francesca Felicia Caputi, Laura Rullo, Serena Stamatakos, Sanzio Candeletti and Patrizia Romualdi
Int. J. Mol. Sci. 2019, 20(6), 1441; https://doi.org/10.3390/ijms20061441 - 21 Mar 2019
Cited by 13 | Viewed by 3260
Abstract
Intracellular signaling mechanisms underlying the opioid system regulation of nociception, neurotransmitters release, stress responses, depression, and the modulation of reward circuitry have been investigated from different points of view. The presence of the ubiquitin proteasome system (UPS) in the synaptic terminations suggest a [...] Read more.
Intracellular signaling mechanisms underlying the opioid system regulation of nociception, neurotransmitters release, stress responses, depression, and the modulation of reward circuitry have been investigated from different points of view. The presence of the ubiquitin proteasome system (UPS) in the synaptic terminations suggest a potential role of ubiquitin-dependent mechanisms in the control of the membrane occupancy by G protein-coupled receptors (GPCRs), including those belonging to the opioid family. In this review, we focused our attention on the role played by the ubiquitination processes and by UPS in the modulation of opioid receptor signaling and in pathological conditions involving the endogenous opioid system. The collective evidence here reported highlights the potential usefulness of proteasome inhibitors in neuropathic pain, addictive behavior, and analgesia since these molecules can reduce pain behavioral signs, heroin self-administration, and the development of morphine analgesic tolerance. Moreover, the complex mechanisms involved in the effects induced by opioid agonists binding to their receptors include the ubiquitination process as a post-translational modification which plays a relevant role in receptor trafficking and degradation. Hence, UPS modulation may offer novel opportunities to control the balance between therapeutic versus adverse effects evoked by opioid receptor activation, thus, representing a promising druggable target. Full article
(This article belongs to the Special Issue Opioid Receptors and Endorphinergic Systems)
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