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δ opioid

Min Li, Stephanie C Tjen-A-Looi, Zhi-Ling Guo, John C Longhurst
Acupuncture lowers blood pressure (BP) in hypertension, but mechanisms underlying its action are unclear. To simulate clinical studies, we performed electroacupuncture (EA) in unanesthetized rats with cold-induced hypertension (CIH) induced by six weeks of cold exposure (6 °C). EA (0.1 - 0.4 mA, 2 Hz) was applied at ST36-37 acupoints overlying the deep peroneal nerve for 30 min twice weekly for five weeks while sham-EA was conducted with the same procedures as EA except for no electrical stimulation...
October 24, 2016: Scientific Reports
Tyler A Johnson, Laura Milan-Lobo, Tao Che, Madeline Ferwerda, Eptisam Lambo, Nicole L McIntosh, Fei Li, Li He, Nicholas Lorig-Roach, Phillip Crews, Jennifer Lynne Whistler
Opioid therapeutics are excellent analgesics, whose utility is compromised by dependence. Morphine (1) and its clinically relevant derivatives such as OxyContin® (4), Vicodin® (5) and Dilaudid® (6) are "biased" agonists at the µ opioid receptor (OR), wherein they engage G-protein signaling but poorly engage β-arrestin and the endocytic machinery. In contrast, the endorphins, met-enkephalin (14) and β-endorphin (15), endogenous peptide agonists for ORs, are more potent analgesics then 1, show reduced liability for tolerance and dependence, and engage both G-protein and β-arrestin pathways as "balanced" agonists...
October 17, 2016: ACS Chemical Neuroscience
Marcin Kunecki, Wojciech Płazak, Tomasz Roleder, Jolanta Biernat, Tomasz Oleksy, Piotr Podolec, Krzysztof Stanisław Gołba
BACKGROUND: Ischemic preconditioning (IPC) and postconditioning (POC) are the novel strategies of attaining cardioprotection against ischemia/reperfusion (I/R) injury. Previous studies suggested the role of opioid pathway, however the class of opioid receptors responsible for this effect in humans remains unknown. The aim of the study was to assess the influence of opioids on simulated I/R injury outcomes in the human myocardium. METHODS: Trabeculae of the human right atrium were electrically driven in organ bath and subjected to simulated I/R injury...
October 13, 2016: Cardiology Journal
Xiao-Su Hu, Clayton A Fisher, Stephanie M Munz, Rebecca L Toback, Thiago D Nascimento, Emily L Bellile, Laura Rozek, Avraham Eisbruch, Francis P Worden, Theodora E Danciu, Alexandre F DaSilva
Patients with head and neck cancer often experience a significant decrease in their quality of life during chemoradiotherapy (CRT) due to treatment-related pain, which is frequently classified as severe. Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. In this pilot study, we investigated the clinical impact and central mechanisms of twenty primary motor cortex (M1) stimulation sessions with tDCS during 7 weeks of CRT for head and neck cancer...
2016: Frontiers in Human Neuroscience
Catherine M Cahill, Wendy Walwyn, Anna M W Taylor, Amynah A A Pradhan, Christopher J Evans
Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanistic differences both between agonists (agonist bias), and between μ- and δ-opioid receptors. In a process we will refer to as pass-forward allostasis, cells modified directly by opioid drugs impute allostatic changes to downstream circuitry...
September 23, 2016: Trends in Pharmacological Sciences
Yang-Chao Wei, Bin Zhang, Xuan Li, Xiao-Meng Liu, Jing Zhang, Biao Lei, Bo Li, Run Zhai, Qian Chen, Yang Li
δ‑opioid receptor (DOR) belongs to the family of G protein‑coupled receptors (GPCRs). Numerous studies have shown that DOR is widely distributed in human peripheral tissues and is closely related to the development and progression of certain malignant tumours. However, there is controversy in the literature regarding whether DOR has an impact on the development and progression of human breast cancer. The present study comprehensively elaborates on the biological functions of DOR by determining the distribution of DOR expression in breast cancer tissues and cells and by further verifying the effects of DOR on breast cancer progression...
September 19, 2016: Oncology Reports
Naama Levy-Cooperman, Gail McIntyre, Laura Bonifacio, Michael McDonnell, J Michael Davenport, Paul S Covington, Leonard S Dove, Edward M Sellers
Drugs with μ-opioid receptor (OR) activity can be associated with abuse and misuse. The peripherally acting mixed μ-OR and κ-OR agonist and δ-OR antagonist, eluxadoline, is approved in the US for the treatment of irritable bowel syndrome with diarrhea. In two separate crossover studies, we evaluated the oral and intranasal abuse potential of eluxadoline versus placebo and the active control oxycodone. Healthy recreational opioid users received eluxadoline 100, 300, and 1000 mg, oxycodone 30 and 60 mg, and placebo (oral study), or eluxadoline 100 and 200 mg, oxycodone 15 and 30 mg, and placebos matched to eluxadoline and oxycodone (intranasal study)...
September 19, 2016: Journal of Pharmacology and Experimental Therapeutics
Wenjuan Tao, Wenjie Zhou, Yuping Wang, Tingting Sun, Haitao Wang, Zhi Zhang, Yan Jin
The efficacy of opioids in patients with chronic neuropathic pain remains controversial. Although activation of δ-opioid receptors (DORs) in the brainstem reduces inflammation-induced persistent hyperalgesia, it is not effective under persistent neuropathic pain conditions and these clinical problems remain largely unknown. In this study, by using a chronic constriction injury (CCI) of the sciatic nerve in rats, we found that in the brainstem nucleus raphe magnus (NRM), DORs emerged on the surface membrane of central synaptic terminals on day 3 after CCI surgery and disappeared on day 14...
September 17, 2016: Neuroscience
Michel E Mickael, Ashish Rajput, Jannetta Steyn, Lyle Wiemerslage, Thomas Bürglin
The comparative genomics between different rhodopsin-like family groups (α, β, γ and δ) is not well studied. We used a combination of phylogenetic analysis and statistical genomic methods to compare rhodopsin-like family proteins in species likely symbolic of this family's evolutionary progression. For intra-cluster relationships, we applied mathematical optimisation to enhance the tree search produced by the neighbour joining method (NJ) and compared it with maximum likelihood (ML) method. To infer inter-clusters relationships, we used Needleman-Wunsch analysis (NW), HHsearch, ancestral sequence reconstruction and phylogenetic network analysis...
September 3, 2016: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
Rossella De Marco, Andrea Bedini, Santi Spampinato, Lorenzo Cavina, Edoardo Pirazzoli, Luca Gentilucci
Recently, the tryptophan-containing noncationizable opioid peptides emerged with atypical structure and unexpected in vivo activity. Herein, we describe analogs of the naturally occurring mixed κ/μ-ligand c[Phe-d-Pro-Phe-Trp] 1 (CJ-15,208). Receptor affinity, selectivity, and agonism/antagonism varied upon enlarging macrocycle size, giving the μ-agonist 9 or the δ-antagonist 10 characterized by low nanomolar affinity. In particular, the μ-agonist c[β-Ala-d-Pro-Phe-Trp] 9 was shown to elicit potent antinociception in a mouse model of visceral pain upon systemic administration...
October 13, 2016: Journal of Medicinal Chemistry
Merve Kasap, Özgür Devrim Can
AIMS: This study was planned to examine the antinociceptive efficacy of agomelatine against acute mechanical, thermal, and chemical nociceptive stimuli, as well as to determine the opioid receptor subtypes mediating these effects. MAIN METHODS: Tail-clip, hot-plate, and acetic acid-induced writhing tests were performed to evaluate anti-nociceptive effect. Besides, possible effect of agomelatine on the motor coordination of animals was assessed with a Rota-rod test...
October 15, 2016: Life Sciences
Stephen J Kohut
Polysubstance abuse is common among substance-use disorder patients, and nicotine is one of the most commonly co-used substances. Epidemiological and clinical laboratory studies suggest that nicotine, when combined with other drugs of abuse, increases intake of one or both substances. This review focuses on the preclinical literature regarding nicotine's interaction with alcohol, stimulants (i.e., cocaine, amphetamines), opioids (i.e., morphine, heroin), and Δ(9)-tetrahydrocannabinol (THC). The current understanding of how these various classes of abused drugs may interact with nicotine on behavioral, physiological, and pharmacological indices that may be important in maintaining co-use of one or both substances in human populations are highlighted...
September 2, 2016: American Journal of Drug and Alcohol Abuse
Wojciech Leppert, Jaroslaw Woron
Opioid-induced constipation (OIC) and other gastrointestinal (GI) symptoms of opioid-induced bowel dysfunction (OIBD) significantly deteriorate patients' quality of life and may lead to noncompliance with opioid schedule and undertreatment of pain. Although traditional oral laxatives are the first-line treatment of OIC, they do not address OIBD pathophysiology, and display numerous adverse effects. OIC treatment includes prokinetics (lubiprostone), opioid switch, and changing route of opioid administration...
September 2016: Therapeutic Advances in Gastroenterology
Feng Zhi, Lian Xue, Naiyuan Shao, Danni Deng, Xuezhi Kang, Dongman Chao, Yuan Xu, Rong Wang, Yilin Yang, Ying Xia
BACKGROUND: Hypoxic/ischemic injury to the heart is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ischemic events, and δ-opioid receptor (DOR) activation is known to protect against hypoxic/ischemic injury, we speculated on the involvement of DOR activation in altering miRNA expression in the heart under hypoxic conditions. The present study aimed to test our hypothesis. METHODS: Male Sprague Dawley rats were exposed to hypoxia (9...
2016: Cellular Physiology and Biochemistry
Fabrizio D''Ovidio, Angelo d''Errico, Elena Farina, Andrea Calvo, Giuseppe Costa, Adriano Chiò
BACKGROUND: An increased frequency of psychotic disorders in amyotrophic lateral sclerosis (ALS) families compared to controls has been reported. Aim of our study was to assess the relationship between nervous system drugs prescriptions and subsequent onset of ALS in a large Italian population. METHODS: The study population consisted of all subjects over 15 years at the 2001 Italian census, resident in Turin since 1996 (n = 687,324), followed up for ALS occurrence from 2002 to 2014...
2016: Neuroepidemiology
Zhe Yi, Shengnan Guo, Xu Hu, Xiaonan Wang, Xiaoqing Zhang, Noreen Griffin, Fengping Shan
Previously it was confirmed that naltrexone, a non-peptide δ-opioid receptor selective antagonist is mainly used for alcoholic dependence and opioid addiction treatment. However, there is increasing data on immune regulation of low dose naltrexone (LDN). The aim of this work was to explore the effect of LDN on the phenotype and function of macrophage. The changes of macrophage after treatment with LDN were examined using flow cytometry (FCM); FITC-dextran phagocytosis and enzyme-linked immunosorbent assay (ELISA)...
October 2016: International Immunopharmacology
Shuang Wu, Sophia R Majeed, Timothy M Evans, Marine D Camus, Nicole M L Wong, Yvette Schollmeier, Minjong Park, Jagan R Muppidi, Andrea Reboldi, Peter Parham, Jason G Cyster, Frances M Brodsky
Clathrin, a cytosolic protein composed of heavy and light chain subunits, assembles into a vesicle coat, controlling receptor-mediated endocytosis. To establish clathrin light chain (CLC) function in vivo, we engineered mice lacking CLCa, the major CLC isoform in B lymphocytes, generating animals with CLC-deficient B cells. In CLCa-null mice, the germinal centers have fewer B cells, and they are enriched for IgA-producing cells. This enhanced switch to IgA production in the absence of CLCa was attributable to increased transforming growth factor β receptor 2 (TGFβR2) signaling resulting from defective endocytosis...
August 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yuan Xu, Feng Zhi, Naiyuan Shao, Rong Wang, Yilin Yang, Ying Xia
The pathological changes of Parkinson's disease (PD) are, at least partially, associated with the dysregulation of PTEN-induced putative kinase 1 (PINK1) and caspase 3. Since hypoxic and neurotoxic insults are underlying causes of PD, and since δ-opioid receptor (DOR) is neuroprotective against hypoxic/ischemic insults, we sought to determine whether DOR activation could protect the cells from damage induced by hypoxia and/or MPP⁺ by regulating PINK1 and caspase 3 expressions. We exposed PC12 cells to either severe hypoxia (0...
2016: International Journal of Molecular Sciences
Juan A Estrada, Mathew A Barlow, Darice Yoshishige, Arthur G Williams, H Fred Downey, Robert T Mallet, James L Caffrey
BACKGROUND: Intermittent hypoxia training (IHT) produces robust myocardial protection against ischemia-reperfusion induced infarction and arrhythmias. Blockade of this cardioprotection by antagonism of either β1-adrenergic or δ-opioid receptors (δ-OR) suggests autonomic and/or opioidergic adaptations. PURPOSE: To test the hypothesis that IHT shifts cardiac autonomic balance toward greater cholinergic and opioidergic influence. METHODS: Mongrel dogs completed 20d IHT, non-hypoxic sham training, or IHT with the δ-OR antagonist naltrindole (200μg/kgsc)...
July 2016: Autonomic Neuroscience: Basic & Clinical
Agata Jarmuż, Martyna Banaszek, Karolina Leń, Martin Storr, Marta Zielińska, Jakub Fichna
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a frequent functional disorder of the gastrointestinal (GI) tract affecting nearly one fifth of the worldwide population. IBS-D is associated with numerous symptoms including diarrhea, bloating, abdominal pain and discomfort, which significantly reduce patients' quality of life. Due to a complex and unclear pathogenesis, effective therapy against IBS-D has not been developed yet. Nowadays, treatment is focused on non-pharmacological (e.g. changes in diet and life style) and pharmacological (e...
August 4, 2016: Mini Reviews in Medicinal Chemistry
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