scholarly journals Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors

2017 ◽  
Vol 32 (1) ◽  
pp. 444-451 ◽  
Author(s):  
Adriano Mollica ◽  
Sveva Pelliccia ◽  
Valeria Famiglini ◽  
Azzurra Stefanucci ◽  
Giorgia Macedonio ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Opioid Peptide ◽  
Hybrid Compound ◽  
Bivalent Ligand

scholarly journals Subcellular Pathways of β-Endorphin Synthesis, Processing, and Release from Immunocytes in Inflammatory Pain

Endocrinology ◽  
2004 ◽  
Vol 145 (3) ◽  
pp. 1331-1341 ◽  
Author(s):  
Shaaban A. Mousa ◽  
Mehdi Shakibaei ◽  
Nicolle Sitte ◽  
Michael Schäfer ◽  
Christoph Stein
Keyword(s):  
Opioid Receptors ◽  
Immune Cells ◽  
Inflammatory Pain ◽  
Secretory Granules ◽  
Inflammatory Cells ◽  
Opioid Peptide ◽  
Active Peptides ◽  
Carboxypeptidase E ◽  
Peripheral Opioid Receptors

Abstract The opioid peptide β-endorphin (END) as well as mRNA for its precursor proopiomelanocortin (POMC) are found not only in the pituitary gland, but also within various types of immune cells infiltrating inflamed sc tissue. During stressful stimuli END is released and interacts with peripheral opioid receptors to inhibit pain. However, the subcellular pathways of POMC processing and END release have not yet been delineated in inflammatory cells. The aim of the present study was to examine the presence of POMC, carboxypeptidase E, the prohormone convertases 1 (PC1), and 2 (PC2), PC2-binding protein 7B2, and the release of END from inflammatory cells in rats. Using immunohistochemistry we detected END and POMC alone or colocalized with PC1, PC2, carboxypeptidase E, and 7B2 in macrophages/monocytes, granulocytes, and lymphocytes of the blood and within inflamed sc paw tissue. Immunoelectron microscopy revealed that END is localized within secretory granules packed in membranous structures in macrophages, monocytes, granulocytes, and lymphocytes. Finally, END is released by noradrenaline from immune cells in vitro. Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules.

21. Effects of opioid peptide agonists selective for μ, δ and κ receptors on identified dorsal horn neurons

1985 ◽  
Vol 308 (1136) ◽  
pp. 427-427 ◽  
Keyword(s):  
Dorsal Horn ◽  
Opioid Receptors ◽  
Opioid Peptide ◽  
Behavioural Responses ◽  
Dorsal Horn Neurons ◽  
Selective Ligands ◽  
Sensory Responses ◽  
Opioid Receptor Agonists ◽  
Thermal Stimuli ◽  
Intrathecal Infusion

The intrathecal infusion of opioid receptor agonists reduces behavioural responses to cutaneous noxious thermal stimuli. Compounds selective for μ- and δ-opioid receptors are clearly effective (Schmauss & Yaksh 1984) but a role for κ receptors is less well established (Han & Xie 1984). The dynorphins, which are present in the dorsal horn, are selective ligands for the K receptor (Corbett et al. 1982). The effects of a dynorphin and those of μ- and δ-selective enkephalin analogues DAGO and DADL, are compared here on the cutaneous sensory responses of single identified dorsal horn neurons whose axons ascend towards supraspinal regions (spinocervical tract, SCT neurons).

Endogenous opioids and related peptides: from molecular biology to clinical medicine The Sir Henry Dale Lecture for 1985

1985 ◽  
Vol 107 (2) ◽  
pp. 147-157 ◽  
Author(s):  
H. Imura ◽  
Y. Kato ◽  
Y. Nakai ◽  
K. Nakao ◽  
I. Tanaka ◽  
...  
Keyword(s):  
Molecular Biology ◽  
Opioid Receptors ◽  
Clinical Medicine ◽  
Biological Activities ◽  
Opioid Peptide ◽  
Endogenous Opioids ◽  
The Body ◽  
Molecular Forms ◽  
Protein Chemistry ◽  
Precursor Proteins

ABSTRACT Advances in techniques in molecular biology have facilitated the research into endogenous opioids and related peptides in several ways. The organization and expression of genes and the primary structure of three precursor proteins of opioid peptides have been elucidated. These studies predicted the presence of potentially bioactive peptides, which has been confirmed by later studies. Advances in techniques in protein chemistry have helped to elucidate the distribution and molecular forms of endogenous opioids and related peptides in the body, and the processing of precursor proteins. Studies on the function of these peptides have shown a broad spectrum of actions. Leumorphin, a newly identified peptide, has been shown to exhibit unique biological activities. In spite of extensive studies, the physiological and pathophysiological significance of opioid peptide systems are not yet completely understood. This is mainly due to the paucity of our knowledge about opioid receptors. Further studies on the subtypes of opioid receptors will help to elucidate all aspects of the function of endogenous opioids and related peptides. J. Endocr. (1985) 107, 147–157

Interaction of Bivalent Ligand KDN21 with Heterodimeric δ-κ Opioid Receptors in Human Embryonic Kidney 293 Cells

2005 ◽  
Vol 68 (4) ◽  
pp. 1079-1086 ◽  
Author(s):  
Zhihua Xie ◽  
Rashmi G. Bhushan ◽  
David J. Daniels ◽  
Philip S. Portoghese
Keyword(s):  
Opioid Receptors ◽  
Human Embryonic Kidney ◽  
Bivalent Ligand ◽  
293 Cells

scholarly journals Electroacupuncture-Induced Dynamic Processes of Gene Expression Levels of Endogenous Opioid Peptide Precursors and Opioid Receptors in the CNS of Goats

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Li-Li Cheng ◽  
Ming-Xing Ding ◽  
Jia Wei ◽  
Yi-Qiang Wu ◽  
Zheng-Ying Qiu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Opioid Receptors ◽  
Pain Threshold ◽  
Opioid Peptide ◽  
Dynamic Processes ◽  
Mrna Levels ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Peptide Precursors ◽  
Nerve System

In order to investigate the dynamic processes of mRNA levels of proenkephalin, proopiomelanocortin, prodynorphin, and opioid receptors (δ-,μ-, andκ-receptor) induced by electroacupuncture (EA) in the central nerve system, goats were stimulated by EA of 60 Hz for 0.5 h at a set of Baihui, Santai, Ergen, and Sanyangluo points. The pain threshold was measured using the method of potassium iontophoresis. The mRNA levels of the three opioid peptide precursors and three opioid receptors were determined with quantitative real-time PCR and the levels of Met-enkephalin with SABC immunohistochemistry at 0.5 h before and at 0, 2, 4, 6, 8, 12, and 24 h after EA. The results showed that the pain threshold correlated (P<0.01) with Met-enkephalin immunoactivities in the measured nuclei and areas of goats. The analgesic aftereffect lasted for 12 h at least. The mRNA levels of the three opioid peptide precursors and three opioid receptors began to increase at 0 h, reached the peak during the time from 4 h to 6 h or at 12 h, and remained higher at 24 h after EA was discontinued. These results suggested that the initiation of gene expression of opioid peptides and the three receptors may be associated with EA-induced analgesic aftereffect.

Increased µ-opioid receptors in sheep brain after transport

1995 ◽  
Vol 1995 ◽  
pp. 204-204
Author(s):  
E.A. Azaga ◽  
R.G. Rodway
Keyword(s):  
Opioid Receptors ◽  
Opioid Peptide ◽  
Brain Regions ◽  
Long Distance ◽  
Long Distance Transport ◽  
The Central Nervous System ◽  
Sheep Brain ◽  
Transport Stress ◽  
Distance Transport ◽  
The Brain

The long distance transport of sheep before slaughter is at present a very important topic in animal welfare. However, Modulation of opioid receptors can be influenced by chronic treatment with opioid agonists and antagonists (Blanchard, and Chang, 1988). Similarly, opioid receptors can be up or down-regulated by stressful stimuli such as restraint, electric footshock or social isolation and housing (Zeman et al., 1988 and Zanella et al., 1991). The present study was carried out to assess the effects of transport stress on the properties of one class of opioid peptide receptor in the brain of sheep after transport stress. Opioid peptides such as β-endorphin are released by the central nervous system during application of stresses such as transport. They are believed to exert analgesic properties and their effectiveness depends partly on the concentration (Bmax) and affinity (Kd) of their receptors. µ-Opioid receptors are found in various brain regions and are selective for endorphins and similar peptides.

scholarly journals Biased Opioid Ligands

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4257 ◽  
Author(s):  
Abdelfattah Faouzi ◽  
Balazs R. Varga ◽  
Susruta Majumdar
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Signal Transduction Pathway ◽  
Opioid Peptide ◽  
Nop Receptor ◽  
Biased Agonism ◽  
Opioid Ligands ◽  
Substance Abuse Disorders ◽  
Δ Opioid Receptor

Achieving effective pain management is one of the major challenges associated with modern day medicine. Opioids, such as morphine, have been the reference treatment for moderate to severe acute pain not excluding chronic pain modalities. Opioids act through the opioid receptors, the family of G-protein coupled receptors (GPCRs) that mediate pain relief through both the central and peripheral nervous systems. Four types of opioid receptors have been described, including the μ-opioid receptor (MOR), κ-opioid receptor (KOR), δ-opioid receptor (DOR), and the nociceptin opioid peptide receptor (NOP receptor). Despite the proven success of opioids in treating pain, there are still some inherent limitations. All clinically approved MOR analgesics are associated with adverse effects, which include tolerance, dependence, addiction, constipation, and respiratory depression. On the other hand, KOR selective analgesics have found limited clinical utility because they cause sedation, anxiety, dysphoria, and hallucinations. DOR agonists have also been investigated but they have a tendency to cause convulsions. Ligands targeting NOP receptor have been reported in the preclinical literature to be useful as spinal analgesics and as entities against substance abuse disorders while mixed MOR/NOP receptor agonists are useful as analgesics. Ultimately, the goal of opioid-related drug development has always been to design and synthesize derivatives that are equally or more potent than morphine but most importantly are devoid of the dangerous residual side effects and abuse potential. One proposed strategy is to take advantage of biased agonism, in which distinct downstream pathways can be activated by different molecules working through the exact same receptor. It has been proposed that ligands not recruiting β-arrestin 2 or showing a preference for activating a specific G-protein mediated signal transduction pathway will function as safer analgesic across all opioid subtypes. This review will focus on the design and the pharmacological outcomes of biased ligands at the opioid receptors, aiming at achieving functional selectivity.

Activation of δ- and κ-opioid receptors by opioid peptides protects cardiomyocytes via KATP channels

2003 ◽  
Vol 285 (3) ◽  
pp. H1032-H1039 ◽  
Author(s):  
Zhiping Cao ◽  
Lijuan Liu ◽  
Donna M. Van Winkle
Keyword(s):  
Cell Death ◽  
Opioid Receptors ◽  
Opioid Peptides ◽  
Trypan Blue ◽  
Area Under The Curve ◽  
Katp Channels ◽  
Opioid Peptide ◽  
Adult Rabbit ◽  
Receptor Specificity ◽  
Selective Antagonist

To examine the receptor specificity and the mechanism of opioid peptide-induced protection, we examined freshly isolated adult rabbit cardiomyocytes subjected to simulated ischemia. Cell death as a function of time was assessed by trypan blue permeability. Dynorphin B (DynB) and Met5-enkephalin (ME) limitation of cell death (expressed as area under the curve) was sensitive to blockade by naltrindole (NTI, a δ-selective antagonist) and 5′-guanidinyl-17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7-2′,3′-indolomorphinan (GNTI dihydrochloride, a κ-selective antagonist): 85.7 ± 2.7 and 142.9 ± 2.7 with DynB and DynB + NTI, respectively ( P < 0.001), 94.1 ± 4.2 and 164.5 ± 7.3 with DynB and DynB + GNTI, respectively ( P < 0.001), 111.9 ± 7.0 and 192.1 ± 6.4 with ME and ME + NTI, respectively ( P < 0.001), and 120.2 ± 4.3 and 170.0 ± 3.3 with ME and ME + GNTI, respectively ( P < 0.001). Blockade of ATP-sensitive K+ channels eliminated DynB- and ME-induced protection: 189.6 ± 5.4 and 139.0 ± 5.4 for control and ME, respectively ( P < 0.001), and 210 ± 5.9 and 195 ± 6.1 for 5-HD and ME + 5-HD, respectively ( P < 0.001); 136.0 ± 5.7 and 63.4 ± 5.4 for control and ME, respectively ( P < 0.001), and 144.6 ± 4.5 and 114.6 ± 7.7 for HMR-1098 and ME + HMR-1098, respectively ( P < 0.01); 189.6 ± 5.4 and 139.0 ± 5.4 for control and ME, respectively ( P < 0.001), and 210 ± 5.9 and 195 ± 6.1 for 5-HD and ME + 5-HD, respectively ( P < 0.001); and 136.0 ± 5.7 and 63.4 ± 5.4 for control and ME, respectively ( P < 0.001), and 144.6 ± 4.5 and 114.6 ± 7.7 for HMR-1098 and ME + HMR-1098, respectively ( P < 0.01). We conclude that opioid peptide-induced cardioprotection is mediated by δ- and κ-receptors and involves sarcolemmal and mitochondrial ATP-sensitive K+ channels.

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