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https://www.readbyqxmd.com/read/28419519/deletion-of-a-distal-rankl-gene-enhancer-delays-progression-of-atherosclerotic-plaque-calcification-in-hypercholesterolemic-mice
#1
Sohel Shamsuzzaman, Melda Onal, Hillary C St John, J Wesley Pike
Receptor activator of NF-κB ligand (RANKL) is a TNFα-like cytokine which mediates diverse physiological functions including bone remodeling and immune regulation. RANKL has been identified in atherosclerotic lesions; however, its role in atherosclerotic plaque development remains elusive. An enhancer located 75kb upstream of the murine RANKL gene's transcription start site designated D5 is important for its calciotropic hormone- and cytokine-mediated expression. Here, we determined the impact of RANKL levels in atherosclerotic plaque development in the D5 enhancer-null (D5(-/-) ) mice in an atherogenic Apoe(-/-) background fed a high-fat diet (HFD)...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28409324/generation-and-characterization-of-polyclonal-and-monoclonal-antibodies-to-human-ntpdase2-including-a-blocking-antibody
#2
Julie Pelletier, Hervé Agonsanou, Ninotchska Delvalle, Michel Fausther, Mabrouka Salem, Brian Gulbransen, Jean Sévigny
Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) is an ectonucleotidase that modulates P2 receptor activation by hydrolyzing ATP to ADP. In rodents, NTPDase2 is expressed by several specialized cell types such as vascular adventitial cells, neuroglial cells, hepatic portal fibroblasts, gustatory type I cells, and cells within the connective tissues of reproductive and gastrointestinal organs. Much less is known regarding the expression and function of NTPDase2 in humans. Here, we developed specific research tools to study human NTPDase2...
April 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28395208/increased-dopamine-receptor-expression-and-anti-depressant-response-following-deep-brain-stimulation-of-the-medial-forebrain-bundle
#3
Manoj P Dandekar, Dustin Luse, Carson Hoffmann, Patrick Cotton, Travis Peery, Christian Ruiz, Caroline Hussey, Vijayasree V Giridharan, Jair C Soares, Joao Quevedo, Albert J Fenoy
BACKGROUND: Among several potential neuroanatomical targets pursued for deep brain stimulation (DBS) for treating those with treatment-resistant depression (TRD), the superolateral-branch of the medial forebrain bundle (MFB) is emerging as a privileged location. We investigated the antidepressant-like phenotypic and chemical changes associated with reward-processing dopaminergic systems in rat brains after MFB-DBS. METHODS: Male Wistar rats were divided into three groups: sham-operated, DBS-Off, and DBS-On...
April 5, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28351853/pharmaceutical-characterization-of-tropomyosin-receptor-kinase-b-agonistic-antibodies-on-human-ips-cell-derived-neurons
#4
Stefanie Traub, Heiko Stahl, Holger Rosenbrock, Eric Simon, Lore Florin, Lisa Hospach, Stefan Hoerer, Ralf Heilker
Brain-derived neurotrophic factor (BDNF) is a central modulator of neuronal development and synaptic plasticity in the central nervous system (CNS). This renders the BDNF-modulated tropomyosin receptor kinase B (TrkB) a promising drug target to treat synaptic dysfunctions. Using GRowth factor-driven expansion and INhibition of NotCH during maturation, the so-called GRINCH neurons were derived from human induced pluripotent stem (hiPS) cells. These GRINCH neurons were employed as model cells for pharmacological profiling of two TrkB-agonistic antibodies, hereafter referred to as AB2 and AB20...
March 28, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28341611/extinction-memory-is-facilitated-by-methylphenidate-and-regulated-by-dopamine-and-noradrenaline-receptors
#5
Cristiane R G Furini, Jonny A K Behling, Carolina G Zinn, Mara Lise Zanini, Eduardo Assis Brasil, Luiza Doro Pereira, Ivan Izquierdo, Jociane de Carvalho Myskiw
Extinction is defined as the learned inhibition of retrieval and is the mainstay of exposure therapy, which is widely used to treat drug addiction, phobias and fear disorders. The psychostimulant, methylphenidate (MPH) is known to increase extracellular levels of noradrenaline and dopamine by blocking their reuptake and studies have demonstrated that MPH can modulate hippocampal physiology and/or functions including long-term potentiation (LTP), learning and memory. However, the influence of MPH on fear extinction memory has been insufficiently studied...
March 21, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28336436/induction-of-dopamine-d1-and-d5-receptors-in-r28%C3%A2-cells-by-light-exposures
#6
Yan Ke, Wentao Li, Zhiqun Tan, Zhikuan Yang
Dopamine is known to play an important role in the pathophysiological process of myopia development relevant to the ambient lighting, but it is still poorly understood about how lighting regulates dopamine and its interaction with dopamine receptors to mediate the pathogenic signal transduction leading to alterations of ocular globe and the pathogenesis of myopia. Many studies have highlighted changes of ocular dopamine amount in response to different lighting conditions, but little attention has been paid to the dopamine receptors during these processes...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28326743/dopamine-receptors-modulate-t-lymphocytes-via-inhibition-of-camp-creb-signaling-pathway
#7
Yan Huang, Can-Can Chen, Ting-Ting Wang, Yi-Hua Qiu, Yu-Ping Peng
OBJECTIVES: We have previously reported that dopamine D2-like receptors including D2, D3 and D4 receptors are more important in mediating modulation of T cells than dopamine D1-like receptors (D1 and D5 receptors). Here we aimed to clarify the role of D2-like receptors in regulation of differentiation and function of T lymphocyte subsets, including helper T (Th)1, Th2, Th17 and regulatory T (Treg) cells. METHODS: Lymphocytes, separated from the mesenteric lymph nodes of mice, were stimulated with concanavalin A (Con A) and treated with the D2-like receptor agonist quinpirole or the antagonist haloperidol...
December 2016: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28301911/the-prevalence-and-clinical-relevance-of-asa-nonresponse-after-cardiac-surgery
#8
Saskia Wand, Elisabeth Hannah Adam, Anna Julienne Wetz, Patrick Meybohm, Nils Kunze-Szikszay, Kai Zacharowski, Aron Frederick Popov, Anton Moritz, Lisa Moldenhauer, Julia Kaiser, Martin Bauer, Christian Friedrich Weber
We aimed to identify the prevalence of acetylsalicylic acid (ASA) nonresponse in patients after coronary artery bypass graft (CABG) surgery and the possible consequences for the rate of major cardiovascular events. This prospective, observational, bicentric cohort study was conducted in two German University hospitals. A total of 400 patients (200 in each study center) undergoing elective CABG surgery were enrolled after written informed consent. Platelet function was analyzed on day 3 (d3) and day 5 (d5) postoperatively following stimulation with arachidonic acid (ASPItest) and with thrombin receptor-activating peptide 6 (TRAPtest) using multiple electrode aggregometry (Multiplate)...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28289242/acupuncture-attenuated-vascular-dementia-induced-hippocampal-long-term-potentiation-impairments-via-activation-of-d1-d5-receptors
#9
Yang Ye, Hui Li, Jing-Wen Yang, Xue-Rui Wang, Guang-Xia Shi, Chao-Qun Yan, Si-Ming Ma, Wen Zhu, Qian-Qian Li, Tian-Ran Li, Ling-Yong Xiao, Cun-Zhi Liu
BACKGROUND AND PURPOSE: Emerging evidence suggests that acupuncture could improve cognitive impairment in vascular dementia by enhancing synaptic plasticity in the hippocampus. The purpose of this study is to investigate whether dopamine, a key mediator of synaptic plasticity, is involved in this cognitive improvement. METHODS: Vascular dementia model was established by bilateral common carotid arteries occlusion in male Wistar rats. Three days after the operation, animals received acupuncture treatment for 2 weeks, once daily...
April 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28253287/platelet-gpiib-supports-initial-pulmonary-retention-but-inhibits-subsequent-proliferation-of-melanoma-cells-during-hematogenic-metastasis
#10
Katrin Echtler, Ildiko Konrad, Michael Lorenz, Simon Schneider, Sebastian Hofmaier, Florian Plenagl, Konstantin Stark, Thomas Czermak, Anca Tirniceriu, Martin Eichhorn, Axel Walch, Georg Enders, Steffen Massberg, Christian Schulz
Platelets modulate the process of cancer metastasis. However, current knowledge on the direct interaction of platelets and tumor cells is mostly based on findings obtained in vitro. We addressed the role of the platelet fibrinogen receptor glycoprotein IIb (integrin αIIb) for experimental melanoma metastasis in vivo. Highly metastatic B16-D5 melanoma cells were injected intravenously into GPIIb-deficient (GPIIb-/-) or wildtype (WT) mice. Acute accumulation of tumor cells in the pulmonary vasculature was assessed in real-time by confocal videofluorescence microscopy...
2017: PloS One
https://www.readbyqxmd.com/read/28214075/asymmetric-total-synthesis-of-tetrahydroprotoberberine-derivatives-and-evaluation-of-their-binding-affinities-at-dopamine-receptors
#11
David Y W Lee, Jing Liu, Shuzhen Zhang, Peng Huang, Lee-Yuan Liu-Chen
Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. l-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites l-ICP, l-CD, and l-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors...
January 31, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28162594/-354-dopamine-d1-d5-receptor-mediated-mechanisms-in-the-maintenance-of-pathological-pain-plasticity
#12
S Megat
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28142338/toxicity-assessment-of-molindone-hydrochloride-a-dopamine-d2-d5-receptor-antagonist-in-juvenile-and-adult-rats
#13
Gopala Krishna, Gopa Gopalakrishnan, Saryu Goel
Neuroleptic drug molindone hydrochloride is a dopamine D2/D5 receptor antagonist and it is in late stage development for the treatment of impulsive aggression in children and adolescents who have attention deficient/hyperactivity disorder (ADHD). This new indication for this drug would expand the target population to include younger patients, and therefore, toxicity assessments in juvenile animals were undertaken in order to determine susceptibility differences, if any, between this age group and the adult rats...
February 20, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28065787/intestinal-farnesoid-x-receptor-controls-transintestinal-cholesterol-excretion-in-mice
#14
Jan Freark de Boer, Marleen Schonewille, Marije Boesjes, Henk Wolters, Vincent W Bloks, Trijnie Bos, Theo H van Dijk, Angelika Jurdzinski, Renze Boverhof, Justina C Wolters, Jan A Kuivenhoven, Jan M van Deursen, Ronald P J Oude Elferink, Antonio Moschetta, Claus Kremoser, Henkjan J Verkade, Folkert Kuipers, Albert K Groen
BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis increasingly is recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) contribute. The mechanisms controlling the flux of cholesterol through the TICE pathway, however, are poorly understood. We aimed to identify mechanisms that regulate and stimulate TICE. METHODS: We performed studies with C57Bl/6J mice, as well as with mice with intestine-specific knockout of the farnesoid X receptor (FXR), mice that express an FXR transgene specifically in the intestine, and ABCG8-knockout mice...
January 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28065748/the-effects-of-early-life-stress-on-dopamine-system-function-in-adolescent-female-rats
#15
Iwona Majcher-Maślanka, Anna Solarz, Krzysztof Wędzony, Agnieszka Chocyk
During adolescence, many neural systems, including the dopamine system, undergo essential remodeling and maturation. It is well known that early-life stress (ELS) increases the risk for many psychopathologies during adolescence and adulthood. It is hypothesized that ELS interferes with the maturation of the dopamine system. There is a sex bias in the prevalence of stress-related mental disorders. Information regarding the effects of ELS on brain functioning in females is very limited. In the current study, maternal separation (MS) procedures were carried out to study the effects of ELS on dopamine system functioning in adolescent female rats...
April 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28060819/an-anti-human-lutheran-glycoprotein-phage-antibody-inhibits-cell-migration-on-laminin-511-epitope-mapping-of-the-antibody
#16
Yurie Enomoto-Okawa, Yuka Maeda, Nozomi Harashima, Yumika Sugawara, Fumihiko Katagiri, Kentaro Hozumi, Kam Man Hui, Motoyoshi Nomizu, Yuji Ito, Yamato Kikkawa
The Lutheran glycoprotein (Lu), also known as basal cell adhesion molecule (B-CAM), is an Ig superfamily (IgSF) transmembrane receptor for laminin α5. Although Lu is not present in normal hepatocytes, its expression is significantly increased in hepatocellular carcinoma (HCC). In this study, we isolated thirteen phage antibodies to Lu from a phage library of peripheral blood from HCC patients, suggesting that these patients produced autoantibodies against endogenous Lu. To characterize the phage antibodies, we determined the Lu domains they recognize...
2017: PloS One
https://www.readbyqxmd.com/read/27930324/dopamine-release-from-the-locus-coeruleus-to-the-dorsal-hippocampus-promotes-spatial-learning-and-memory
#17
Kimberly A Kempadoo, Eugene V Mosharov, Se Joon Choi, David Sulzer, Eric R Kandel
Dopamine neurotransmission in the dorsal hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal hippocampus originate from neurons of the locus coeruleus (LC)...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27825624/quantification-of-suvorexant-in-urine-using-gas-chromatography-mass-spectrometry
#18
Mariah Carson, Sarah Kerrigan
Suvorexant (Belsomra(®)) is a novel sedative hypnotic drug that is prescribed to promote sleep in patients with insomnia. It is the first of a new class of drugs classified as dual orexin receptor antagonists (DORAs). Sedative hypnotics with central nervous system depressant effects feature prominently in forensic toxicology investigations. For this reason, a new analytical method was developed to identify suvorexant in urine using liquid-liquid extraction (LLE) and gas chromatography/mass spectrometry (GC/MS)...
January 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27817026/the-inhibition-of-dopamine-synthesis-in-fetuses-changes-the-pattern-of-t-lymphocyte-maturation-in-the-thymus-of-adult-rats
#19
N V Lifantseva, Ts O Koneeva, S N Voronova, L A Zakharova, V I Melnikova
The mRNA for dopamine receptors of type D1, D3, D5, but not type D2, was detected in the thymus of rats starting from day 16 of embryonic development (E16). Dopamine at concentrations of 10(-8)-10(‒6) M inhibited fetus thymocyte response to mitogen, confirming the functionality of the receptors and the possibility of a direct effect of dopamine on the developing thymus. Pharmacological inhibition of catecholamine synthesis in the crucial period of thymus development leads to long-term changes in the T-system immunity due to increased production of natural regulatory T-lymphocytes...
September 2016: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27811173/an-allosteric-potentiator-of-the-dopamine-d1-receptor-increases-locomotor-activity-in-human-d1-knock-in-mice-without-causing-stereotypy-or-tachyphylaxis
#20
Kjell A Svensson, Beverly A Heinz, John M Schaus, James P Beck, Junliang Hao, Joseph H Krushinski, Matthew R Reinhard, Michael P Cohen, Sarah L Hellman, Brian G Getman, Xushan Wang, Michelle M Menezes, Deanna L Maren, Julie F Falcone, Wesley H Anderson, Rebecca A Wright, S Michelle Morin, Kelly L Knopp, Benjamin L Adams, Borys Rogovoy, Ilya Okun, Todd M Suter, Michael A Statnick, Donald R Gehlert, David L Nelson, Virginia L Lucaites, Renee Emkey, Neil W DeLapp, Todd R Wiernicki, Jeffrey W Cramer, Charles R Yang, Robert F Bruns
Allosteric potentiators amplify the sensitivity of physiologic control circuits, a mode of action that could provide therapeutic advantages. This hypothesis was tested with the dopamine D1 receptor potentiator DETQ [2-(2,6-dichlorophenyl)-1-((1S,3R)-3-(hydroxymethyl)-5-(2-hydroxypropan-2-yl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one]. In human embryonic kidney 293 (HEK293) cells expressing the human D1 receptor, DETQ induced a 21-fold leftward shift in the cAMP response to dopamine, with a Kb of 26 nM...
January 2017: Journal of Pharmacology and Experimental Therapeutics
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