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https://www.readbyqxmd.com/read/28648913/the-effects-of-analgesics-on-central-processing-of-tonic-pain-a-cross-over-placebo-controlled-study
#1
Dina Lelic, Tine M Hansen, Esben B Mark, Anne E Olesen, Asbjørn M Drewes
INTRODUCTION: Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat moderate to severe pain, but the central mechanisms underlying their analgesia remain unclear. This study investigated how brain activity at rest and exposed to tonic pain is modified by oxycodone (opioid) and venlafaxine (SNRI). METHODS: Twenty healthy males were included in this randomized, cross-over, double-blinded study. 61-channel electroencephalogram (EEG) was recorded before and after five days of treatment with placebo, oxycodone (10 mg extended release b...
June 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28647372/delta-opioid-receptor-agonist-attenuates-lipopolysaccharide-induced-myocardial-injury-by-regulating-autophagy
#2
Pin Zhao, Jianke Kuai, Jinjian Gao, Li Sun, Yan Wang, Linong Yao
BACKGROUND: Previous studies have described the protective effects of DADLE on myocardial injury in sepsis. Recently, autophagy has been shown to be an innate defense mechanism in sepsis-related myocardial injury. However, whether DADLE has an pro-autophagic effect is yet to be elucidated. The present study aimed to investigate the effect of DADLE on the regulation of autophagy during sepsis. METHODS: Male mice were subjected to LPS or vehicle intraperitoneal injection...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28645621/two-delta-opioid-receptor-subtypes-are-functional-in-single-ventral-tegmental-area-neurons-and-can-interact-with-the-mu-opioid-receptor
#3
Elyssa B Margolis, Wakako Fujita, Lakshmi A Devi, Howard L Fields
The mu and delta opioid receptors (MOR and DOR) are highly homologous members of the opioid family of GPCRs. There is evidence that MOR and DOR interact, however the extent to which these interactions occur in vivo and affect synaptic function is unknown. There are two stable DOR subtypes: DPDPE sensitive (DOR1) and deltorphin II sensitive (DOR2); both are blocked by DOR selective antagonists. Robust motivational effects are produced by local actions of both MOR and DOR ligands in the ventral tegmental area (VTA)...
June 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28566554/pi3k-class-ii-%C3%AE-regulates-%C3%AE-opioid-receptor-export-from-the-trans-golgi-network
#4
Daniel J Shiwarski, Marlena Darr, Cheryl A Telmer, Marcel P Bruchez, Manojkumar A Puthenveedu
The interplay between signaling and trafficking by G protein-coupled receptors (GPCRs) has focused mainly on endocytic trafficking. Whether and how surface delivery of newly synthesized GPCRs is regulated by extracellular signals is less understood. Here we define a signaling-regulated checkpoint at the trans-Golgi network (TGN) that controls the surface delivery of the delta opioid receptor (δR). In PC12 cells, inhibition of Phosphoinositide-3 Kinase (PI3K) activity blocked export of newly synthesized δR from the Golgi and delivery to the cell surface, similar to treatment with Nerve Growth Factor (NGF)...
May 31, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28564576/the-endocannabinoid-system-as-a-target-for-addiction-treatment-trials-and-tribulations
#5
REVIEW
Matthew E Sloan, Joshua L Gowin, Vijay A Ramchandani, Yasmin L Hurd, Bernard Le Foll
Addiction remains a major public health concern, and while pharmacotherapies can be effective, clinicians are limited by the paucity of existing interventions. Endocannabinoid signaling is involved in reward and addiction, which raises the possibility that drugs targeting this system could be used to treat substance use disorders. This review discusses findings from randomized controlled trials evaluating cannabinergic medications for addiction. Current evidence suggests that pharmacotherapies containing delta-9-tetrahydrocannabinol, such as dronabinol and nabiximols, are effective for cannabis withdrawal...
May 28, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28558327/d-alanine-2-leucine-5-enkephaline-dadle-mediated-dor-activation-augments-human-hucb-bfs-viability-subjected-to-oxidative-stress-via-attenuation-of-the-upr
#6
Madhubanti Mullick, Katari Venkatesh, Dwaipayan Sen
Human mesenchymal stem cells (hMSCs) although being potent in repairing injured or ischemic tissues, their success regarding tissue-regenerative approaches are hindered by the paucity in their viability. The elevated levels of reactive oxygen species (ROS) in damaged sites provoke the pernicious effects of donor MSC survival. In the present study, the effect of delta-opioid receptor (DOR) activation on human umbilical cord-blood borne fibroblasts (hUCB-BFs) survival under oxidative stress (H2O2) was evaluated...
May 24, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28554003/opioids-and-opioid-receptors-orchestrate-wound-repair
#7
Ying Wang, Mihir Gupta, Tasneem Poonawala, Mariya Farooqui, Yunfang Li, Fei Peng, Sheldon Rao, Michael Ansonoff, John E Pintar, Kalpna Gupta
We have previously shown that topical opioids including morphine and its congeners promote healing of full thickness ischemic wounds in rats. We examined the contribution of mu opioid receptor (MOPr)-mediated healing of full thickness ischemic wounds using MOPr and delta or kappa opioid receptor knockout (KO) mice. Wound closure in the early (day 5) as well as later phases was delayed in topical morphine or PBS-treated MOPr-KO mice compared with reciprocal treatments of wounds in wild-type (WT) mice. MOPr expression was significantly upregulated at 30 min in the wound margins and colocalized with wound margins and vasculature in the epidermal and dermal layers of the skin...
May 18, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28522254/novel-delta-opioid-receptor-agonists-with-oxazatricyclodecane-structure-showing-potent-agonistic-activities
#8
Kohei Hayashida, Shigeto Hirayama, Takashi Iwai, Yoshikazu Watanabe, Toshihiro Takahashi, Junichi Sakai, Eriko Nakata, Tomio Yamakawa, Hideaki Fujii, Hiroshi Nagase
We recently reported oxazatricyclodecane derivatives 1 as δ opioid receptor (DOR) agonists having a novel chemotype, but their DOR agonistic activities were relatively low. Based on the working hypothesis that the dioxamethylene moiety in 1 may be an accessory site and that it may interfere with the sufficient conformational change of the receptor required for exerting the full agonistic responses, we designed and synthesized new oxazatricyclodecane derivatives 2-4 lacking the dioxamethylene moiety. As we expected, the designed compounds 2-4 showed pronouncedly improved agonistic activities for the DOR...
June 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28510066/the-delta-opioid-receptor-in-pain-control
#9
Khaled Abdallah, Louis Gendron
Nowadays, the delta opioid receptor (DOPr) represents a promising target for the treatment of chronic pain and emotional disorders. Despite the fact that they produce limited antinociceptive effects in healthy animals and in most acute pain models, DOPr agonists have shown efficacy in various chronic pain models. In this chapter, we review the progresses that have been made over the last decades in understanding the role played by DOPr in the control of pain. More specifically, the distribution of DOPr within the central nervous system and along pain pathways is presented...
May 17, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28509375/chronic-nicotine-induced-changes-in-gene-expression-of-delta-and-kappa-opioid-receptors-and-their-endogenous-ligands-in-the-mesocorticolimbic-system-of-the-rat
#10
Muzeyyen Ugur, Egemen Kaya, Oguz Gozen, Ersin O Koylu, Lutfiye Kanit, Aysegul Keser, Burcu Balkan
Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are proposed as important mediators of nicotine reward. The present study investigated the regulatory effect of chronic nicotine treatment on the gene expression of DOR, KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were injected subcutaneously with nicotine at doses of 0.2, 0.4 or 0.6 mg/kg/day for six days. Rats were decapitated one hour after the last dose on day six, as this timing coincides with increased dopamine release in the mesocorticolimbic system...
May 16, 2017: Synapse
https://www.readbyqxmd.com/read/28475363/new-tetranorlabdanoic-acid-from-aerial-parts-of-salvia-aethiopis
#11
Radhakrishnan Srivedavyasasri, Miriah B White, Tatyana S Kustova, Nadezhda G Gemejiyeva, Charles L Cantrell, Samir A Ross
Salvia aethiopis is a perennial plant native to Eurasia and known by the common names Mediterranean sage or African sage. This plant has been used in Iranian medicine as a carminative and tonic. The ethanolic extract of aerial part of S. aethiopis exhibited moderate to weak activity towards delta and kappa opioid receptors (46.3 and 45.3% displacement, respectively). Chromatographic purification of the ethanolic extract on silica gel column led to isolation of one new: 3α-hydroxy-8α-acetoxy-13,14,15,16-tetranorlabdan-12-oic acid (I) and three known compounds: sesquiterpene spathulenol (II), β-sitosterol (III) and β-sitosterol-3-O-glucoside (IV)...
May 5, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28465374/regulation-of-%C3%AE-opioid-receptor-mediated-signaling-and-antinociception-in-peripheral-sensory-neurons-by-arachidonic-acid-dependent-12-15-lipoxygenase-metabolites
#12
Laura C Sullivan, Teresa A Chavera, Xiaoli Gao, Miryam M Pando, Kelly A Berg
The function of δ opioid receptors (DOR) expressed by peripheral pain-sensing neurons (nociceptors) is regulated by both cyclooxygenase- and lipoxygenase (LOX)-dependent arachidonic acid (AA) metabolites. Whereas cyclooxygenase metabolites enhance responsiveness, LOX metabolites elicit a refractory, nonsignaling state of the DOR receptor system for antinociceptive signaling. In this study, using high-performance liquid chromatography-tandem mass spectrometry analyses, we have found that the 12-/15-LOX metabolites, 12-hydroxyeicosatetraenoic acid (HETE) and 15-HETE, were elevated after treatment of adult rat primary sensory neuron cultures with AA...
July 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28462718/rubiscolins-highly-potent-peptides-derived-from-plant-proteins
#13
Renata Perlikowska, Anna Janecka
Rubiscolins are two naturally occurring, linear peptides, isolated from the pepsin digests of D-ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) from spinach leaves. Their sequences are as follows: Tyr-Pro-Leu-Asp-Leu (YPLDL, rubiscolin-5) and Tyr-Pro-Leu-Asp-Leu-Phe (YPLDLF, rubiscolin-6, also known as rubixyl). Though their structure does not resemble typical opioid peptides, rubiscolins were found to exhibit high affinity and selectivity for the delta opioid receptor and an antinociceptive effect in mice after oral administration...
April 26, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28455226/the-effect-of-selective-opioid-receptor-agonists-and-antagonists-on-epileptiform-activity-in-morphine-dependent-infant-mice-hippocampal-slices
#14
Yousef Panahi, Ehsan Saboory, Ali Rassouli, Goudarz Sadeghi-Hashjin, Shiva Roshan-Milani, Leila Derafshpour, Yousef Rasmi
Hippocampal slices of mouse brain were used to estimate how selective agonist and antagonist of opioid receptors alter Low-Mg(+2) artificial cerebrospinal fluid (LM-ACSF)-induced epileptiform activities in normal and morphine-dependent mice. Brain slices were obtained from control and morphine-dependent mice. The morphine-dependent group received morphine once a day for 5 consecutive days, and the control group received saline. All injections were administered subcutaneously (s.c) in a volume of 0.1mL on postnatal days 14-18...
August 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28446883/in-vitro-and-in-vivo-profile-of-ppl-101-and-ppl-103-mixed-opioid-partial-agonist-analgesics-with-low-abuse-potential
#15
Taline V Khroyan, Andrea Cippitelli, Nicholas Toll, John A Lawson, William Crossman, Willma E Polgar, Lawrence Toll
Opiates are still the most effective and widely used treatments for acute and chronic pain. However, the problems associated with morphine and other standard opioid analgesics severely limit their effectiveness in the clinic. PPL-101 and PPL-103 derived from morphine and morphinan ring systems contain a chiral N-substituent, which confers it with a unique combination of high-binding affinities and partial agonist activities at mu, delta, and kappa opioid receptors, leading to unique in vivo pharmacology compared to other conventional opioids...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28440739/featured-article-pharmacological-postconditioning-with-delta-opioid-attenuates-myocardial-reperfusion-injury-in-isolated-porcine-hearts
#16
Maria Seewald, James A Coles, Daniel C Sigg, Paul A Iaizzo
Ischemic preconditioning has been utilized to protect the heart from ischemia prior to ischemia onset, whereas postconditioning is employed to minimize the consequences of ischemia at the onset of reperfusion. The underlying mechanisms and pathways of ischemic pre- and postconditioning continue to be investigated as therapeutic targets. We evaluated the administration of a delta opioid agonist or cariporide on various parameters associated with myocardial reperfusion injury upon reperfusion of isolated porcine hearts...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28431630/kynurenic-acid-and-its-analogue-can-alter-the-opioid-receptor-g-protein-signaling-after-acute-treatment-via-nmda-receptor-in-rat-cortex-and-striatum
#17
Reza Samavati, Ferenc Zádor, Edina Szűcs, Bernadett Tuka, Diána Martos, Gábor Veres, Róbert Gáspár, István M Mándity, Ferenc Fülöp, László Vécsei, Sándor Benyhe, Anna Borsodi
Previously, we have shown that the N-methyl d-aspartate (NMDA)-receptor antagonist kynurenic acid (KYNA) and its analogue KYNA1 do not bind directly to mu, kappa and delta opioid receptors in vitro. On the other hand, chronic administration of KYNA and KYNA1 resulted in region (cortex vs striatum) and opioid receptor-type specific alterations in G-protein activation of mouse brain homogenates. Here we describe for the first time the acute effect of KYNA and KYNA1 on opioid receptor function with the possible involvement of the NMDA receptor...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28407740/mu-opioid-receptor-and-delta-opioid-receptor-differentially-regulate-microglial-inflammatory-response-to-control-proopiomelanocortin-neuronal-apoptosis-in-the-hypothalamus-effects-of-neonatal-alcohol
#18
Pallavi Shrivastava, Miguel A Cabrera, Lucy G Chastain, Nadka I Boyadjieva, Shaima Jabbar, Tina Franklin, Dipak K Sarkar
BACKGROUND: Opioid receptors are known to control neurotransmission of various peptidergic neurons, but their potential role in regulation of microglia and neuronal cell communications is unknown. We investigated the role of mu-opioid receptors (MOR) and delta-opioid receptors (DOR) on microglia in the regulation of apoptosis in proopiomelanocortin (POMC) neurons induced by neonatal ethanol in the hypothalamus. METHODS: Neonatal rat pups were fed a milk formula containing ethanol or control diets between postnatal days 2-6...
April 14, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28381559/identification-of-a-signaling-cascade-that-maintains-constitutive-%C3%AE-opioid-receptor-incompetence-in-peripheral-sensory-neurons
#19
Allison Doyle Brackley, Shayda Sarrami, Ruben Gomez, Kristi A Guerrero, Nathaniel A Jeske
μ-Opioid receptor (MOR) agonists are often used to treat severe pain but can result in adverse side effects. To circumvent systemic side effects, targeting peripheral opioid receptors is an attractive alternative treatment for severe pain. Activation of the δ-opioid receptor (DOR) produces similar analgesia with reduced side effects. However, until primed by inflammation, peripheral DOR is analgesically incompetent, raising interest in the mechanism. We recently identified a novel role for G-protein-coupled receptor kinase 2 (GRK2) that renders DOR analgesically incompetent at the plasma membrane...
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28364251/allosteric-modulation-model-of-the-mu-opioid-receptor-by-herkinorin-a-potent-not-alkaloidal-agonist
#20
A F Marmolejo-Valencia, K Martínez-Mayorga
Modulation of opioid receptors is the primary choice for pain management and structural information studies have gained new horizons with the recently available X-ray crystal structures. Herkinorin is one of the most remarkable salvinorin A derivative with high affinity for the mu opioid receptor, moderate selectivity and lack of nitrogen atoms on its structure. Surprisingly, binding models for herkinorin are lacking. In this work, we explore binding models of herkinorin using automated docking, molecular dynamics simulations, free energy calculations and available experimental information...
March 31, 2017: Journal of Computer-aided Molecular Design
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