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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
#1
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...
November 29, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27891289/nor-bni-antagonism-of-kappa-opioid-agonist-induced-reinstatement-of-ethanol-seeking-behavior
#2
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
#3
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-kappa-opioid-receptor
#4
Cyf N Ramos-Colon, Yeon Sun Lee, Michael Vincent Remesic, Sara M Hall, Justin LaVigne, Peg Davis, Alexander J Sandweiss, Mary I McIntosh, Jessica Hanson, Tally M Largent-Milnes, Todd W Vanderah, John M Streicher, Frank Porreca, Victor J Hruby
Dynorphin A (Dyn A) is an endogenous ligand for the opioid receptors with preference for the kappa 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...
October 31, 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
#5
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
#6
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
#7
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
#8
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
#9
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...
October 6, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27754872/expanding-the-role-of-tachykinins-in-the-neuroendocrine-control-of-reproduction
#10
Chrysanthi Fergani, Victor Navarro
Reproductive function is driven by the hormonal interplay between the gonads and brain-pituitary axis. Gonadotropin-releasing hormone (GnRH) is released in a pulsatile manner, which is critical for the attainment and maintenance of fertility, however, GnRH neurons lack the ability to directly respond to most regulatory factors, and a hierarchical upstream neuronal network governs its secretion. We and others proposed a model in which Kiss1 neurons in the arcuate nucleus (ARC), so called KNDy neurons, release kisspeptin (a potent GnRH secretagogue) in a pulsatile manner to drive GnRH pulses under the coordinated autosynaptic action of its cotransmitters, the tachykinin neurokinin B (NKB, stimulatory) and dynorphin (inhibitory)...
October 17, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27717401/adoptive-transfer-of-m2-macrophages-reduces-neuropathic-pain-via-opioid-peptides
#11
Maria Pannell, Dominika Labuz, Melih Ö Celik, Jacqueline Keye, Arvind Batra, Britta Siegmund, Halina Machelska
BACKGROUND: During the inflammation which occurs following nerve damage, macrophages are recruited to the site of injury. Phenotypic diversity is a hallmark of the macrophage lineage and includes pro-inflammatory M1 and anti-inflammatory M2 populations. Our aim in this study was to investigate the ability of polarized M0, M1, and M2 macrophages to secrete opioid peptides and to examine their relative contribution to the modulation of neuropathic pain. METHODS: Mouse bone marrow-derived cells were cultured as unstimulated M0 macrophages or were stimulated into an M1 phenotype using lipopolysaccharide and interferon-γ or into an M2 phenotype using interleukin-4...
October 7, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27699938/kappa-opioid-antagonists-for-psychiatric-disorders-from-bench-to-clinical-trials
#12
William A Carlezon, Andrew D Krystal
Kappa-opioid receptor (KOR) antagonists are currently being considered for the treatment of a variety of neuropsychiatric conditions, including depressive, anxiety, and substance abuse disorders. A general ability to mitigate the effects of stress, which can trigger or exacerbate these conditions, may explain their putative efficacy across such a broad array of conditions. The discovery of their potentially therapeutic effects evolved from preclinical research designed to characterize the molecular mechanisms by which experience causes neuroadaptations in the nucleus accumbens (NAc), a key element of brain reward circuitry...
October 2016: Depression and Anxiety
https://www.readbyqxmd.com/read/27688945/kappa-opioid-receptors-differentially-regulate-low-and-high-levels-of-ethanol-intake-in-female-mice
#13
Ashlee Van't Veer, Karen L Smith, Bruce M Cohen, William A Carlezon, Anita J Bechtholt
INTRODUCTION: Studies in laboratory animals and humans indicate that endogenous opioids play an important role in regulating the rewarding value of various drugs, including ethanol (EtOH). Indeed, opioid antagonists are currently a front-line treatment for alcoholism in humans. Although roles for mu- and delta-opioid receptors have been characterized, the contribution of kappa-opioid receptors (KORs) is less clear. There is evidence that changes in KOR system function can decrease or increase EtOH drinking, depending on test conditions...
September 2016: Brain and Behavior
https://www.readbyqxmd.com/read/27619237/discovery-of-stable-non-opioid-dynorphin-a-analogues-interacting-at-the-bradykinin-receptors-for-the-treatment-of-neuropathic-pain
#14
Sara M Hall, Lindsay LeBaron, Cyf Ramos-Colon, Chaoling Qu, Jennifer Yanhua Xie, Frank Porreca, Josephine Lai, Yeon Sun Lee, Victor J Hruby
Dynorphin A (Dyn A) is a unique endogenous ligand that possesses well-known neuroinhibitory effects via opioid receptors with a preference for the kappa receptor but also neuroexcitatory effects, which cause hyperalgesia. We have shown that the neuroexcitatory effects are mediated through bradykinin (BK) receptors and that intrathecal (i.th.) administration of our lead ligand 1, [des-Arg(7)]-Dyn A-(4-11), which shows good binding affinity (IC50 = 150 nM) at the BK receptors, blocks Dyn A-induced hyperalgesia in naïve animals and reverses thermal and tactile hypersensitivities in a dose-dependent manner in nerve-injured animals...
September 27, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27605249/distinct-roles-of-exogenous-opioid-agonists-and-endogenous-opioid-peptides-in-the-peripheral-control-of-neuropathy-triggered-heat-pain
#15
Dominika Labuz, Melih Ö Celik, Andreas Zimmer, Halina Machelska
Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27577933/bullatine-a-stimulates-spinal-microglial-dynorphin-a-expression-to-produce-anti-hypersensitivity-in-a-variety-of-rat-pain-models
#16
Qian Huang, Xiao-Fang Mao, Hai-Yun Wu, Teng-Fei Li, Ming-Li Sun, Hao Liu, Yong-Xiang Wang
BACKGROUND: Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao) has been prescribed to manage chronic pain, arthritis, and traumatic injuries. Bullatine A, a C20-diterpenoid alkaloid, is one of its principle effective compounds. This study aimed to investigate the anti-hypersensitivity of bullatine A in a variety of rat pain models and explore its mechanisms of action. METHODS: Rat neuropathic pain, inflammatory pain, diabetic neuropathic pain, and bone cancer pain models were used...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27568355/role-of-dynorphin-in-hypoxic-pulmonary-hypertension
#17
Juan Li, Xiaojie Liang, Yaguang Zhou, Shumiao Zhang, Fan Yang, Haitao Guo, Rong Fan, Na Feng, Min Jia, Yueming Wang, Mingchao Liu, Jianming Pei
Previously study showed κ-opioid receptor stimulation with exogenous κ-opioid receptor agonist elicited a protective effect against hypoxic pulmonary hypertension (HPH). However, the effect of endogenous κ-opioid receptor agonist dynorphin A on HPH remains unclear. This study was to determine the role of dynorphin in HPH. Hypoxia for 2 weeks induced HPH. Compared with the HPH group, the HPH + nor-BNI (a selective κ-opioid receptor antagonist) group showed a significant increase in mean pulmonary arterial pressure (mPAP)...
August 25, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27567942/involvement-of-the-dynorphin-kor-system-on-the-nociceptive-emotional-and-cognitive-manifestations-of-joint-pain-in-mice
#18
Roger Negrete, María Salud García Gutiérrez, Jorge Manzanares, Rafael Maldonado
Joint pain is a major clinical problem mainly associated to osteoarthritis, and characterized by articular cartilage degradation resulting in a complex chronic pain state that includes nociceptive, emotional and cognitive manifestations. Memory impairment, depressive- and anxiety-like symptoms have been reported to be associated with chronic pain, leading to a decrease of life quality. In this study, we evaluated the involvement of the endogenous dynorphin/kappa opioid receptor (KOR) system on the nociceptive, emotional, cognitive, neurochemical and epigenetic manifestations of joint pain...
August 24, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27549338/high-frequency-stimulation-induced-peptide-release-synchronizes-arcuate-kisspeptin-neurons-and-excites-gnrh-neurons
#19
Jian Qiu, Casey C Nestor, Chunguang Zhang, Stephanie L Padilla, Richard D Palmiter, Martin J Kelly, Oline K Rønnekleiv
Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1(ARH)) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1(ARH) neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice...
2016: ELife
https://www.readbyqxmd.com/read/27543746/prenatal-testosterone-exposure-decreases-colocalization-of-insulin-receptors-in-kisspeptin-neurokinin-b-dynorphin-and-agouti-related-peptide-neurons-of-the-adult-ewe
#20
Maria Cernea, Rebecca Phillips, Vasantha Padmanabhan, Lique M Coolen, Michael N Lehman
Insulin serves as a link between the metabolic and reproductive systems, communicating energy availability to the hypothalamus and enabling reproductive mechanisms. Adult Suffolk ewes prenatally exposed to testosterone (T) display an array of reproductive and metabolic dysfunctions similar to those seen in women with polycystic ovarian syndrome (PCOS), including insulin resistance. Moreover, prenatal T treatment alters neuropeptide expression in KNDy (co-expressing kisspeptin, neurokinin B/dynorphin) and agouti-related peptide (AgRP) neurons in the arcuate nucleus, two populations that play key roles in the control of reproduction and metabolism, respectively...
October 2016: European Journal of Neuroscience
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