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https://www.readbyqxmd.com/read/28097228/kappa-opioid-receptor-signaling-protects-cartilage-tissue-against-posttraumatic-degeneration
#1
Ling Wu, Shu Zhang, Ruzanna Shkhyan, Siyoung Lee, Francesca Gullo, Claire D Eliasberg, Frank A Petrigliano, Kai Ba, Jing Wang, Yunfeng Lin, Denis Evseenko
Osteoarthritis is the most common form of arthritis, and pain relief with opioid-like drugs is a commonly used therapeutic for osteoarthritic patients. Recent studies published by our group showed that the kappa opioid receptor (KOR) is highly expressed during human development in joint-forming cells. However, the precise role of this receptor in the skeletal system remains elusive. The main aim of the current study was to investigate the role of KOR signaling in synovial and cartilaginous tissues in pathological conditions...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28091903/effects-of-opioid-peptides-on-changes-in-lipid-metabolism-in-rats-subjected-to-swimming-stress
#2
A V Solin, A Yu Lyashev, Yu D Lyashev
Blood levels of nonesterified fatty acids, total cholesterol, triglycerides, and LDL increased in rats subjected to forced swimming stress. Administration of opioid peptides dynorphin A(1-13), DSLET, or DAGO reduced stress-induced disturbances in lipid metabolism. Dynorphin A(1-13) and DAGO produced the most pronounced effects and prevented an increase in concentrations of nonesterified fatty acids, triglycerides, total cholesterol, and LDL as soon as 39 h after treatment. Only DSLET increased HDL content in the plasma of stressed rats...
January 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28069442/novel-signaling-of-dynorphin-at-%C3%AE%C2%BA-opioid-receptor-bradykinin-b2-receptor-heterodimers
#3
Bingyuan Ji, Haiqing Liu, Rumin Zhang, Yunlu Jiang, Chunmei Wang, Sheng Li, Jing Chen, Bo Bai
The κ-opioid receptor (KOR) and bradykinin B2 receptor (B2R) are involved in a variety of important physiological processes and share many similar characteristics in terms of their distribution and functions in the nervous system. We first demonstrated the endogenous expression of KOR and B2R in human SH-SY5Y cells and their co-localization on the membrane of human embryonic kidney 293 (HEK293) cells. Bioluminescence and fluorescence resonance energy transfer and the proximity ligation assay were exploited to demonstrate the formation of functional KOR and B2R heteromers in transfected cells...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28056342/pathway-and-cell-specific-kappa-opioid-receptor-modulation-of-excitation-inhibition-balance-differentially%C3%A2-gates-d1-and-d2-accumbens-neuron-activity
#4
Hugo A Tejeda, Jocelyn Wu, Alana R Kornspun, Marco Pignatelli, Vadim Kashtelyan, Michael J Krashes, Brad B Lowell, William A Carlezon, Antonello Bonci
Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic KOR inhibition decreases the excitatory drive of D1 MSN activity by the amygdala, but not the hippocampus...
January 4, 2017: Neuron
https://www.readbyqxmd.com/read/28050629/antireward-compulsivity-and-addiction-seminal-contributions-of-dr-athina-markou-to-motivational-dysregulation-in-addiction
#5
REVIEW
George F Koob
RATIONALE AND OBJECTIVES: Addiction is defined as a chronically relapsing disorder characterized by compulsive drug seeking that is hypothesized to derive from multiple sources of motivational dysregulation. METHODS AND RESULTS: Dr. Athina Markou made seminal contributions to our understanding of the neurobiology of addiction with her studies on the dysregulation of reward function using animal models with construct validity. Repeated overstimulation of the reward systems with drugs of abuse decreases reward function, characterized by brain stimulation reward and presumbably reflecting dysphoria-like states...
January 3, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28049031/the-efficacy-of-dynorphin-fragments-at-the-%C3%AE%C2%BA-%C3%AE-and-%C3%AE-opioid-receptor-in-transfected-hek-cells-and-in-an-animal-model-of-unilateral-peripheral-inflammation
#6
M Morgan, A Heffernan, F Benhabib, S Wagner, A K Hewavitharana, P N Shaw, P J Cabot
Dynorphin 1-17 is an endogenous peptide that is released at sites of inflammation by leukocytes, binding preferentially to κ-opioid receptors (KOP) to mediate nociception. We have previously shown that dynorphin 1-17 is rapidly biotransformed to smaller peptide fragments in inflamed tissue homogenate. This study aimed to determine the efficacy and potency of selected dynorphin fragments produced in an inflamed environment at the KOP, μ and δ-opioid receptors (MOP and DOP respectively) and in a model of inflammatory pain...
December 31, 2016: Peptides
https://www.readbyqxmd.com/read/28009489/effects-of-orchidectomy-and-testosterone-replacement-on-numbers-of-kisspeptin-neurokinin-b-and-dynorphin-a-immunoreactive-neurons-in-the-arcuate-nucleus-of-the-hypothalamus-in-obese-and-diabetic-rats
#7
M Dudek, P A Kołodziejski, E Pruszyńska-Oszmałek, K Ziarniak, J H Sliwowska
Neurons expressing kisspeptin, neurokinin B, and dynorphin A, located in the arcuate nucleus of the hypothalamus (ARC), are important regulators of reproduction. Their functions depend on metabolic and hormonal status. We hypothesized that male rats with high-fat diet-induced obesity (DIO) and/or streptozotocin-induced diabetes mellitus type 1 (DM1) and type 2 (DM2) will have: 1) alterations in numbers of immunoreactive (ir) cells: kisspeptin-ir and/or neurokinin B-ir, and dynorphin A-ir neurons in the ARC in the sham condition; 2) orchidectomy alone (ORX) and with testosterone treatment (ORX+T) will unmask possible deficits in the response of these neurons in DIO, and/or DM1 and DM2 rats...
December 23, 2016: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/27998058/label-free-neuroproteomics-of-the-hippocampal-accumbal-circuit-reveals-deficits-in-neurotransmitter-and-neuropeptide-signaling-in-mice-lacking-ethanol-sensitive-adenosine-transporter
#8
Alfredo Oliveros, Phillip Starski, Daniel Lindberg, Sun Choi, Carrie J Heppelmann, Surendra Dasari, Doo-Sup Choi
The neural circuit of the dorsal hippocampus (dHip) and nucleus accumbens (NAc) contributes to cue-induced learning and addictive behaviors, as demonstrated by the escalation of ethanol-seeking behaviors observed following deletion of the adenosine equilibrative nucleoside transporter 1 (ENT1-/-) in mice. Here, we perform a quantitative LC-MS/MS neuroproteomics in the dHip and NAc of ENT1-/- mice. Using Ingenuity Pathway Analysis, we identified proteins associated with increased long-term potentiation, ARP2/3-mediated actin cytoskeleton signaling...
December 20, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27989838/opioid-gene-expression-changes-and-post-translational-histone-modifications-at-promoter-regions-in-the-rat-nucleus-accumbens-after-acute-and-repeated-3-4-methylenedioxy-methamphetamine-mdma-exposure
#9
Francesca Felicia Caputi, Martina Palmisano, Lucia Carboni, Sanzio Candeletti, Patrizia Romualdi
The recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) has been shown to produce neurotoxic damage and long-lasting changes in several brain areas. In addition to the involvement of serotoninergic and dopaminergic systems, little information exists about the contribution of nociceptin/orphaninFQ (N/OFQ)-NOP and dynorphin (DYN)-KOP systems in neuronal adaptations evoked by MDMA. Here we investigated the behavioral and molecular effects induced by acute (8mg/kg) or repeated (8mg/kg twice daily for seven days) MDMA exposure...
October 29, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27989510/concurrent-bullatine-a-enhances-morphine-antinociception-and-inhibits-morphine-antinociceptive-tolerance-by-indirect-activation-of-spinal-%C3%AE%C2%BA-opioid-receptors
#10
Qian Huang, Ming-Li Sun, Yuan Chen, Xin-Yan Li, Yong-Xiang Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Bullatine A, a C20-diterpenoid alkaloid and one of the major effective ingredients in Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao), can block pain hypersensitivity in a variety of rodent models through expression of spinal microglial dynorphin A. AIM OF THE STUDY: To assess the interaction between bullatine A and morphine on antinociception in acute nociception and pain hypersensitivity states, with the exogenous synthetic dynorphin A as a comparison MATERIALS AND METHODS: Spinal nerve ligation-induced neuropathic rats and naïve mice were used for assessing the acute and chronic interactions of bullatine A/dynorphin A with morphine...
January 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27982437/commentary-unhealthy-diet-nutrient-status-and-adhd-symptoms-a-confounding-role-for-environmental-nitrous-oxide-exposure-reflections-on-rijlaarsdam-et%C3%A2-al-2016
#11
Keith Fluegge
Rijlaarsdam et al. (2016) recently published their findings utilizing a longitudinal design showing that prenatal 'unhealthy diet' was positively associated with IGF2 DNA methylation at birth across both youth cohorts. However, only in the EOP youth was prenatal 'unhealthy diet' positively associated with ADHD symptoms presumably through IGF2 DNA hypermethylation. Rijlaarsdam et al.'s () choice to assess high fat and sugar diet with the Food Frequency Questionnaire (FFQ) may offer some indication as to prenatal nutrient status, as the foods identified by the FFQ in their study are relatively low in free choline...
January 2017: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/27913257/prodynorphin-and-kappa-opioid-receptor-mrna-expression-in-the-brain-relates-to-social-status-and-behavior-in-male-european-starlings
#12
Lauren V Riters, Melissa A Cordes, Sharon A Stevenson
Numerous animal species display behavioral changes in response to changes in social status or territory possession. For example, in male European starlings only males that acquire nesting sites display high rates of sexual and agonistic behavior. Past studies show that mu and delta opioid receptors regulate behaviors associated with social ascension or defeat. Opioids also act at kappa receptors, with dynorphin binding with the highest affinity; however, the role of these opioids in social behavior has not been well studied...
March 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27891289/nor-bni-antagonism-of-kappa-opioid-agonist-induced-reinstatement-of-ethanol-seeking-behavior
#13
Erin Harshberger, Emily A Gilson, Kelli Gillett, Jasmine H Stone, Laila El Amrani, Glenn R Valdez
Recent work suggests that the dynorphin (DYN)/kappa opioid receptor (KOR) system may be a key mediator in the behavioral effects of alcohol. The objective of the present study was to examine the ability of the KOR antagonist norbinaltorphimine (nor-BNI) to attenuate relapse to ethanol seeking due to priming injections of the KOR agonist U50,488 at time points consistent with KOR selectivity. Male Wistar rats were trained to self-administer a 10% ethanol solution, and then responding was extinguished. Following extinction, rats were injected with U50,488 (0...
2016: Journal of Addiction
https://www.readbyqxmd.com/read/27842940/nalmefene-for-the-management-of-alcohol-dependence-review-on-its-pharmacology-mechanism-of-action-and-meta-analysis-on-its-clinical-efficacy
#14
Karl Mann, Lars Torup, Per Sørensen, Antoni Gual, Robert Swift, Brendan Walker, Wim van den Brink
Nalmefene, a mu- and delta-opioid receptor (MOR, DOR) antagonist and a partial kappa-opioid receptor (KOR) agonist, is approved in the European Union and other countries for the reduction of alcohol consumption in alcohol dependent patients with a high drinking risk level according to WHO ("target population"). This review presents an overview of nalmefene׳s pharmacology, its mechanisms of action and a meta-analysis on its efficacy in reducing alcohol consumption. The review was based on a systematic search of the literature...
December 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27797517/structure-activity-relationships-of-des-arg-7-dynorphin-a-analogues-at-the-%C3%AE%C2%BA-opioid-receptor
#15
Cyf N Ramos-Colon, Yeon Sun Lee, Michael Remesic, Sara M Hall, Justin LaVigne, Peg Davis, Alexander J Sandweiss, Mary I McIntosh, Jessica Hanson, Tally M Largent-Milnes, Todd W Vanderah, John Streicher, Frank Porreca, Victor J Hruby
Dynorphin A (Dyn A) is an endogenous ligand for the opioid receptors with preference for the κ opioid receptor (KOR), and its structure-activity relationship (SAR) has been extensively studied at the KOR to develop selective potent agonists and antagonists. Numerous SAR studies have revealed that the Arg(7) residue is essential for KOR activity. In contrast, our systematic SAR studies on [des-Arg(7)]Dyn A analogues found that Arg(7) is not a key residue and even deletion of the residue does not affect biological activities at the KOR...
November 23, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27796753/promotion-of-the-unfolding-protein-response-in-orexin-dynorphin-neurons-in-sudden-infant-death-syndrome-sids-elevated-pperk-and-atf4-expression
#16
Nicholas J Hunt, Karen A Waters, Rita Machaalani
We previously demonstrated that sudden infant death syndrome (SIDS) infants have decreased orexin immunoreactivity within the hypothalamus and pons compared to non-SIDS infants. In this study, we examined multiple mechanisms that may promote loss of orexin expression including programmed cell death, impaired maturation/structural stability, neuroinflammation and impaired unfolding protein response (UPR). Immunofluorescent and immunohistochemical staining for a number of markers was performed in the tuberal hypothalamus and pons of infants (1-10 months) who died from SIDS (n = 27) compared to age- and sex-matched non-SIDS infants (n = 19)...
October 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27796511/neuromolecular-imaging-a-nanobiotechnology-for-parkinson-s-disease-advancing-pharmacotherapy-for-personalized-medicine
#17
P A Broderick, L Wenning, Y-S Li
Evaluating each patient and animal as its own control achieves personalized medicine, which honors the hippocratic philosophy, explaining that "it is far more important to know what person has the disease than what disease the person has." Similarly, individualizing molecular signaling directly from the patient's brain in real time is essential for providing prompt, patient-based treatment as dictated by the point of care. Fortunately, nanotechnology effectively treats many neurodegenerative diseases. In particular, the new medicinal frontier for the discovery of therapy for Parkinson's disease is nanotechnology and nanobiotechnology...
October 28, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27761113/ester-hydrolysis-differentially-reduces-aconitine-induced-anti-hypersensitivity-and-acute-neurotoxicity-involvement-of-spinal-microglial-dynorphin-expression-and-implications-for-aconitum-processing
#18
Teng-Fei Li, Nian Gong, Yong-Xiang Wang
Aconitines, including bulleyaconitine A, probably the most bioactive and abundant alkaloids in Aconitum plant, are a group of diester C19-diterpenoid alkaloids with one acetylester group attached to C8 of the diterpenoid skeleton and one benzoylester group to C14. Hydrolysis of both groups is involved in the processing of Aconitum, a traditional Chinese medicinal approach. We recently demonstrated that bulleyaconitine A produced anti-hypersensitivity, which was mediated by stimulation of spinal microglial dynorphin A expression...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27760914/erratum-j-reprod-dev-vol-59-no-3-p-266-272-dynorphin-kappa-opioid-receptor-signaling-partly-mediates-estrogen-negative-feedback-effect-on-lh-pulses-in-female-rats
#19
Mst Parvin Mostari, Nahoko Ieda, Chikaya Deura, Shiori Minabe, Shunji Yamada, Yoshihisa Uenoyama, Kei-Ichiro Maeda, Hiroko Tsukamura
Figure 3(a) have been corrected.
2016: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/27756562/cyclic-non-opioid-dynorphin-a-analogues-for-the-bradykinin-receptors
#20
Yeon Sun Lee, Michael Remesic, Cyf Ramos-Colon, Sara M Hall, Alexander Kuzmin, David Rankin, Frank Porreca, Josephine Lai, Victor J Hruby
Nerve injury and inflammation cause up-regulation of an endogenous opioid ligand, dynorphin A (Dyn A), in the spinal cord resulting in hyperalgesia via the interaction with bradykinin receptors (BRs). This is a non-opioid neuroexcitatory effect that cannot be blocked by opioid antagonists. Our systematic structure-activity relationships study on Dyn A identified lead ligands 1 and 4, along with the key structural feature (i.e. amphipathicity) for the BRs. However, the ligands showed very low metabolic stability in plasma (t1/2 <1h) and therefore, in order to improve their metabolic stabilities with retained biological activities, various modifications were performed...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
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