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https://www.readbyqxmd.com/read/28214075/asymmetric-total-synthesis-of-tetrahydroprotoberberine-derivatives-and-evaluation-of-their-binding-affinities-at-dopamine-receptors
#1
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
#2
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
#3
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...
January 31, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28065787/intestinal-farnesoid-x-receptor-controls-transintestinal-cholesterol-excretion-in-mice
#4
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 is increasingly 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 are, however, poorly understood. We aimed to identify mechanisms that regulate and stimulate TICE. METHODS: We performed studies with C57Bl/6J mice, as well as 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
#5
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...
January 5, 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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27793671/antiferroptotic-activity-of-non-oxidative-dopamine
#11
Ding Wang, Yingpeng Peng, Yangchun Xie, Borong Zhou, Xiaofang Sun, Rui Kang, Daolin Tang
Dopamine is a neurotransmitter that has many functions in the nervous and immune systems. Ferroptosis is a non-apoptotic form of regulated cell death that is involved in cancer and neurodegenerative diseases. However, the role of dopamine in ferroptosis remains unidentified. Here, we show that the non-oxidative form of dopamine is a strong inhibitor of ferroptotic cell death. Dopamine dose-dependently blocked ferroptosis in cancer (PANC1 and HEY) and non-cancer (MEF and HEK293) cells following treatment with erastin, a small molecule ferroptosis inducer...
October 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27725799/loss-of-catecholaminergic-neuromodulation-of-persistent-forms-of-hippocampal-synaptic-plasticity-with-increasing-age
#12
Hannah Twarkowski, Denise Manahan-Vaughan
Neuromodulation by means of the catecholaminergic system is a key component of motivation-driven learning and behaviorally modulated hippocampal synaptic plasticity. In particular, dopamine acting on D1/D5 receptors and noradrenaline acting on beta-adrenergic receptors exert a very potent regulation of forms of hippocampal synaptic plasticity that last for very long-periods of time (>24 h), and occur in conjunction with novel spatial learning. Antagonism of these receptors not only prevents long-term potentiation (LTP) and long-term depression (LTD), but prevents the memory of the spatial event that, under normal circumstances, leads to the perpetuation of these plasticity forms...
2016: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/27721791/dopamine-d1-d5-but-not-d2-d3-receptor-dependency-of-synaptic-plasticity-at-hippocampal-mossy-fiber-synapses-that-is-enabled-by-patterned-afferent-stimulation-or-spatial-learning
#13
Hardy Hagena, Denise Manahan-Vaughan
Although the mossy fiber (MF) synapses of the hippocampal CA3 region display quite distinct properties in terms of the molecular mechanisms that underlie synaptic plasticity, they nonetheless exhibit persistent (>24 h) synaptic plasticity that is akin to that observed at the Schaffer collateral (SCH)-CA1 and perforant path (PP)-dentate gyrus (DG) synapses of freely behaving rats. In addition, they also respond to novel spatial learning with very enduring forms of long-term potentiation (LTP) and long-term depression (LTD)...
2016: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/27609280/dopaminergic-receptors-and-adrenoceptors-in-circulating-lymphocytes-as-putative-biomarkers-for-the-early-onset-and-progression-of-multiple-sclerosis
#14
Marco Cosentino, Mauro Zaffaroni, Massimiliano Legnaro, Raffaella Bombelli, Laura Schembri, Damiano Baroncini, Anna Bianchi, Raffaella Clerici, Mario Guidotti, Paola Banfi, Giorgio Bono, Franca Marino
Clinically isolated syndrome (CIS) is a first, usually recovering, episode of neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects might benefit from early disease-modifying drugs, provided that those at high risk of developing MS can be identified. Gene expression for dopaminergic receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS patients and is affected by treatment with interferon (IFN)-β. In particular, lymphocyte DR D5 mRNA might be a marker of IFN-β response in MS patients...
September 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27602521/locus-coeruleus-and-dopaminergic-consolidation-of-everyday-memory
#15
Tomonori Takeuchi, Adrian J Duszkiewicz, Alex Sonneborn, Patrick A Spooner, Miwako Yamasaki, Masahiko Watanabe, Caroline C Smith, Guillén Fernández, Karl Deisseroth, Robert W Greene, Richard G M Morris
The retention of episodic-like memory is enhanced, in humans and animals, when something novel happens shortly before or after encoding. Using an everyday memory task in mice, we sought the neurons mediating this dopamine-dependent novelty effect, previously thought to originate exclusively from the tyrosine-hydroxylase-expressing (TH(+)) neurons in the ventral tegmental area. Here we report that neuronal firing in the locus coeruleus is especially sensitive to environmental novelty, locus coeruleus TH(+) neurons project more profusely than ventral tegmental area TH(+) neurons to the hippocampus, optogenetic activation of locus coeruleus TH(+) neurons mimics the novelty effect, and this novelty-associated memory enhancement is unaffected by ventral tegmental area inactivation...
September 15, 2016: Nature
https://www.readbyqxmd.com/read/27597526/validation-of-an-improved-scale-for-rating-l-dopa-induced-dyskinesia-in-the-mouse-and-effects-of-specific-dopamine-receptor-antagonists
#16
Irene Sebastianutto, Natallia Maslava, Corey R Hopkins, M Angela Cenci
Rodent models of l-DOPA-induced dyskinesia (LID) are essential to investigate pathophysiological mechanisms and treatment options. Ratings of abnormal involuntary movements (AIMs) are used to capture both qualitative and quantitative features of dyskinetic behaviors. Thus far, validated rating scales for the mouse have anchored the definition of severity to the time during which AIMs are present. Here we have asked whether the severity of axial, limb, and orolingual AIMs can be objectively assessed with scores based on movement amplitude...
September 2, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27541930/modulation-of-dopaminergic-pathways-to-treat-erectile-dysfunction
#17
REVIEW
Ulf Simonsen, Simon Comerma-Steffensen, Karl-Erik Andersson
The currently recommended first-line treatments of erectile dysfunction (ED), phosphodiesterase type 5 inhibitors (PDE5i), for example sildenafil, are efficacious in many patients with ED of vascular origin, but this therapy is insufficient in approximately 30-40% of men with ED where there is also a neuronal affection. There is a demand of novel approaches to treat the condition. We review the possibility of modulating the dopaminergic pathways to improve erectile function. Dopamine D1 (D1 , D5 )- and D2 (D2 -D4 )-like receptors in the paraventricular area, the medial pre-optic area, the spinal cord, and in the erectile tissue are involved in erection, and several agonists developed for the treatment of Parkinson's disease are associated with increased libido...
October 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27533478/3-dicyanomethylidene-indan-1-one-functionalized-calix-4-arene-calix-4-pyrrole-hybrid-an-ion-pair-sensor-for-cesium-salts
#18
Yerim Yeon, Soojung Leem, Corin Wagen, Vincent M Lynch, Sung Kuk Kim, Jonathan L Sessler
A chromogenic calix[4]arene-calix[4]pyrrole hybrid ion pair receptor bearing an indane substituent at a β-pyrrolic position has been prepared. On the basis of solution-phase UV-vis spectroscopic analysis and (1)H NMR spectroscopic studies carried out in 10% methanol in chloroform, receptor 1 is able to bind only cesium ion pairs (e.g., CsF, CsCl, and CsNO3) but not the constituent cesium cation (as its perchlorate salt) or the F(-), Cl(-), or NO3(-) anions (as the tetrabutylammonium salts). It thus displays rudimentary AND logic gate behavior...
September 2, 2016: Organic Letters
https://www.readbyqxmd.com/read/27525724/kinetic-mrna-profiling-in-a-rat-model-of-left-ventricular-hypertrophy-reveals-early-expression-of-chemokines-and-their-receptors
#19
Simona Nemska, Laurent Monassier, Max Gassmann, Nelly Frossard, Reza Tavakoli
Left-ventricular hypertrophy (LVH), a risk factor for heart failure and death, is characterized by cardiomyocyte hypertrophy, interstitial cell proliferation, and leukocyte infiltration. Chemokines interacting with G protein-coupled chemokine receptors may play a role in LVH development by promoting recruitment of activated leukocytes or modulating left-ventricular remodeling. Using a pressure overload-induced kinetic model of LVH in rats, we examined during 14 days the expression over time of chemokine and chemokine receptor mRNAs in left ventricles from aortic-banded vs sham-operated animals...
2016: PloS One
https://www.readbyqxmd.com/read/27470093/differential-involvement-of-ca-2-calmodulin-dependent-protein-kinases-and-mitogen-activated-protein-kinases-in-the-dopamine-d1-d5-receptor-mediated-potentiation-in-hippocampal-ca1-pyramidal-neurons
#20
Mahesh Shivarama Shetty, Sreedharan Sajikumar
Dopaminergic neurotransmission modulates and influences hippocampal CA1 synaptic plasticity, learning and long-term memory mechanisms. Investigating the mechanisms involved in the slow-onset potentiation induced by the dopamine D1/D5 receptor agonists in hippocampal CA1 region, we have reported recently that it could play a role in regulating synaptic cooperation and competition. We have also shown that a sustained activation of MEK/MAP kinase pathway was involved in the maintenance of this long-lasting potentiation (Shivarama Shetty, Gopinadhan, & Sajikumar, 2016)...
July 25, 2016: Neurobiology of Learning and Memory
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