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https://www.readbyqxmd.com/read/29326120/macrophage-scavenger-receptor-sr-ai-contributes-to-the-clearance-of-von-willebrand-factor
#1
Nikolett Wohner, Vincent Muczynski, Amel Mohamadi, Paulette Legendre, Gabriel Aymé, Olivier D Christophe, Peter J Lenting, Cécile V Denis, Caterina Casari
Previously, we identified LDL-receptor related protein-1 on macrophages to mediate shear stress-dependent clearance of von Willebrand factor. In control experiments, however, we observed that von Willebrand factor also binds to macrophages independently of this receptor under static conditions, suggesting the existence of additional clearance-receptors. In search for such receptors, we focused on the macrophage-specific scavenger-receptor SR-AI. Von Willebrand factor displays efficient binding to SR-AI (half-max binding 14+/-5 nM)...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29298375/single-molecule-force-spectroscopy-reveals-two-domain-binding-mode-of-pilus-1-tip-protein-rrga-of-streptococcus-pneumoniae-to-fibronectin
#2
Tanja D Becke, Stefan Ness, Raimund Gürster, Arndt F Schilling, Anne-Marie di Guilmi, Stefanie Sudhop, Markus Hilleringmann, Hauke Clausen-Schaumann
For host cell adhesion and invasion, surface piliation procures benefits for bacteria. A detailed investigation of how pili adhere to host cells is therefore a key aspect in understanding their role during infection. Streptococcus pneumoniae TIGR 4, a clinical relevant serotype 4 strain, is capable of expressing pilus-1 with terminal RrgA, an adhesin interacting with host extracellular matrix (ECM) proteins. We used single molecule force spectroscopy to investigate the binding of full length RrgA and single RrgA domains to fibronectin...
January 3, 2018: ACS Nano
https://www.readbyqxmd.com/read/29281965/is-dopamine-transporter-mediated-dopaminergic-signaling-in-the-retina-a-noninvasive-biomarker-for-attention-deficit-hyperactivity-disorder-a-study-in-a-novel-dopamine-transporter-variant-val559-transgenic-mouse-model
#3
Heng Dai, Chad R Jackson, Gwynne L Davis, Randy D Blakely, Douglas G McMahon
BACKGROUND: Dopamine (DA) is a critical neuromodulator in the retina. Disruption of retinal DA synthesis and signaling significantly attenuates light-adapted, electroretinogram (ERG) responses, as well as contrast sensitivity and acuity. As these measures can be detected noninvasively, they may provide opportunities to detect disease processes linked to perturbed DA signaling. Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes...
December 28, 2017: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/29223348/distinctive-binding-properties-of-the-negative-allosteric-modulator-3h-sb269-652-at-recombinant-dopamine-d3-receptors
#4
Irene Fasciani, Ilaria Pietrantoni, Mario Rossi, Clotilde Mannoury la Cour, Gabriella Aloisi, Francesco Marampon, Marco Scarselli, Mark J Millan, Roberto Maggio
Recently, employing radioligand displacement and functional coupling studies, we demonstrated that SB269,652 (N-[(1r,4r)-4-[2-(7-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-1H-indole-2-carboxamide) interacts in an atypical manner with dopamine D3 receptor displaying a unique profile reminiscent of a negative allosteric ligand. Here, we characterized the binding of radiolabelled [3H]SB269,652 to human dopamine D3 receptor stably expressed in Chinese Hamster Ovary cells. Under saturating conditions, SB269,652 showed a KD value of ≈ 1nM...
December 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29221470/potential-diagnostic-markers-of-olanzapine-efficiency-for-acute-psychosis-a-focus-on-peripheral-biogenic-amines
#5
A E Taraskina, R F Nasyrova, A M Zabotina, D N Sosin, К А Sosina, E E Ershov, M N Grunina, E M Krupitsky
BACKGROUND: Biomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients...
December 8, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/29180730/gpcrs-crystal-structure-of-d4-dopamine-receptor
#6
Sarah Crunkhorn
No abstract text is available yet for this article.
November 28, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29171915/targeting-hypersensitive-corticostriatal-terminals-in-restless-legs-syndrome
#7
Gabriel Yepes, Xavier Guitart, William Rea, Amy H Newman, Richard P Allen, Christopher J Earley, César Quiroz, Sergi Ferré
OBJECTIVE: The first aim was to demonstrate a previously hypothesized increased sensitivity of corticostriatal glutamatergic terminals in the rodent with brain iron deficiency (BID), a pathogenetic model of restless legs syndrome (RLS). The second aim was to determine whether these putative hypersensitive terminals could constitute a significant target for drugs effective in RLS, including dopamine agonists (pramipexole and ropinirole) and α2 δ ligands (gabapentin). METHODS: A recently introduced in vivo optogenetic-microdialysis approach was used, which allows the measurement of the extracellular concentration of glutamate upon local light-induced stimulation of corticostriatal glutamatergic terminals...
November 24, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29149620/the-dopamine-d4-receptor-gene-birth-weight-maternal-depression-maternal-attention-and-the-prediction-of-disorganized-attachment-at-36-months-of-age-a-prospective-gene%C3%A3-environment-analysis
#8
Justin Graffi, Ellen Moss, Alexia Jolicoeur-Martineau, Gal Moss, Vanessa Lecompte, Katherine Pascuzzo, Vanessa Babineau, Cathryn Gordon-Green, Viara R Mileva-Seitz, Klaus Minde, Roberto Sassi, Meir Steiner, James L Kennedy, Helene Gaudreau, Robert Levitan, Michael J Meaney, Ashley Wazana
BACKGROUND: Efforts to understand the developmental pathways for disorganized attachment reflect the importance of disorganized attachment on the prediction of future psychopathology. The inconsistent findings on the prediction of disorganized attachment from the dopamine D4 receptor (DRD4) gene, birth weight, and maternal depression as well as the evidence supporting the contribution of early maternal care, suggest the importance of exploring a gene by environment model. METHODS: Our sample is from the Maternal Adversity, Vulnerability, and Neurodevelopment project; consisting of 655 mother-child dyads...
November 14, 2017: Infant Behavior & Development
https://www.readbyqxmd.com/read/29138490/bidirectional-modulation-of-hippocampal-synaptic-plasticity-by-dopaminergic-d4-receptors-in-the-ca1-area-of-hippocampus
#9
Sheeja Navakkode, Katherine C M Chew, Sabrina Jia Ning Tay, Qingshu Lin, Thomas Behnisch, Tuck Wah Soong
Long-term potentiation (LTP) is the persistent increase in the strength of the synapses. However, the neural networks would become saturated if there is only synaptic strenghthening. Synaptic weakening could be facilitated by active processes like long-term depression (LTD). Molecular mechanisms that facilitate the weakening of synapses and thereby stabilize the synapses are also important in learning and memory. Here we show that blockade of dopaminergic D4 receptors (D4R) promoted the formation of late-LTP and transformed early-LTP into late-LTP...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29119585/effects-of-dopamine-receptor-antagonist-antipsychotic-therapy-on-blood-pressure
#10
REVIEW
N H Gonsai, V H Amin, C G Mendpara, R Speth, G M Hale
WHAT IS KNOWN AND OBJECTIVE: Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of hypertension is multifaceted and difficult to identify. Dopamine receptors, especially those in the kidneys, play a role in blood pressure regulation, and alterations in their function can cause hypertension. The objective of this review was to investigate the association between the use of dopamine antagonists with hypertension focusing especially on second-generation antipsychotics, like clozapine that is D4 receptor antagonist...
November 8, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29106549/the-in-vitro-actions-of-loxapine-on-dopaminergic-and-serotonergic-receptors-time-to-consider-atypical-classification-of-this-antipsychotic-drug
#11
Florian Ferreri, Dominique Drapier, Emmanuelle Baloche, Mehemed Ouzid, Luc Zimmer, Pierre-Michel Llorca
Background: The denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule's relevant modes of action. Method: Competition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D1 to D5, 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [ 11C]-Raclopride [18F]-Altanserin [18F]-MPPF [11C]-SB207145 and [18F]-2FNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29101232/isopeptide-and-ester-bond-ubiquitination-both-regulate-degradation-of-the-human-dopamine-receptor-4
#12
Jennifer C Peeler, Sophia Schedin-Weiss, Mariluz Soula, Manija A Kazmi, Thomas P Sakmar
How an optimal level of human dopamine D4 receptor (hD4R) is maintained in synaptic membranes is not known. We show here that hD4R is ubiquitinated in primary neurons. We go on to show that ubiquitin is attached to hD4R through isopeptide and ester bonds. When lysine (Lys) residues of the hD4R are substituted with arginine (Arg) residues, cellular D4R protein levels increase. A synergistic effect on D4R levels is noted when cytoplasmic serine (Ser) and threonine (Thr) residues are mutated. Chloroquine, an inhibitor of lysosomal degradation, did not have an effect on hD4R protein levels...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29095852/neuronal-correlates-of-ketamine-and-walking-induced-gamma-oscillations-in-the-medial-prefrontal-cortex-and-mediodorsal-thalamus
#13
Katrina E Furth, Alex J McCoy, Caroline Dodge, Judith R Walters, Andres Buonanno, Claire Delaville
Alterations in the function of the medial prefrontal cortex (mPFC) and its major thalamic source of innervation, the mediodorsal (MD) thalamus, have been hypothesized to contribute to the symptoms of schizophrenia. The NMDAR antagonist ketamine, used to model schizophrenia, elicits a brain state resembling early stage schizophrenia characterized by cognitive deficits and increases in cortical low gamma (40-70 Hz) power. Here we sought to determine how ketamine differentially affects spiking and gamma local field potential (LFP) activity in the rat mPFC and MD thalamus...
2017: PloS One
https://www.readbyqxmd.com/read/29054088/the-interactions-among-organophosphate-pesticide-exposure-oxidative-stress-and-genetic-polymorphisms-of-dopamine-receptor-d4-increase-the-risk-of-attention-deficit-hyperactivity-disorder-in-children
#14
Chia-Huang Chang, Ching-Jung Yu, Jung-Chieh Du, Hsien-Chih Chiou, Hsin-Chang Chen, Winnie Yang, Ming-Yi Chung, Ying-Sheue Chen, Betau Hwang, I-Fang Mao, Mei-Lien Chen
OBJECTIVE: The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. METHODS: This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified...
October 17, 2017: Environmental Research
https://www.readbyqxmd.com/read/29051383/d4-dopamine-receptor-high-resolution-structures-enable-the-discovery-of-selective-agonists
#15
Sheng Wang, Daniel Wacker, Anat Levit, Tao Che, Robin M Betz, John D McCorvy, A J Venkatakrishnan, Xi-Ping Huang, Ron O Dror, Brian K Shoichet, Bryan L Roth
Dopamine receptors are implicated in the pathogenesis and treatment of nearly every neuropsychiatric disorder. Although thousands of drugs interact with these receptors, our molecular understanding of dopaminergic drug selectivity and design remains clouded. To illuminate dopamine receptor structure, function, and ligand recognition, we determined crystal structures of the D4 dopamine receptor in its inactive state bound to the antipsychotic drug nemonapride, with resolutions up to 1.95 angstroms. These structures suggest a mechanism for the control of constitutive signaling, and their unusually high resolution enabled a structure-based campaign for new agonists of the D4 dopamine receptor...
October 20, 2017: Science
https://www.readbyqxmd.com/read/29046641/buspirone-counteracts-mk-801-induced-schizophrenia-like-phenotypes-through-dopamine-d3-receptor-blockade
#16
Sebastiano Alfio Torrisi, Salvatore Salomone, Federica Geraci, Filippo Caraci, Claudio Bucolo, Filippo Drago, Gian Marco Leggio
Background: Several efforts have been made to develop effective antipsychotic drugs. Currently, available antipsychotics are effective on positive symptoms, less on negative symptoms, but not on cognitive impairment, a clinically relevant dimension of schizophrenia. Drug repurposing offers great advantages over the long-lasting, risky and expensive, de novo drug discovery strategy. To our knowledge, the possible antipsychotic properties of buspirone, an azapirone anxiolytic drug marketed in 1986 as serotonin 5-HT1A receptor (5-HT1AR) partial agonist, have not been extensively investigated despite its intriguing pharmacodynamic profile, which includes dopamine D3 (D3R) and D4 receptor (D4R) antagonist activity...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29017837/robo-ig4-is-a-dimerization-domain
#17
Galit Yom-Tov, Reut Barak, Omri Matalon, Mira Barda-Saad, Julia Guez-Haddad, Yarden Opatowsky
Robo receptors play pivotal roles in axonal guidance as well as in neurogenesis, angiogenesis, cell migration, and cancer progression and invasiveness. They are considered to be attractive drug targets for the treatment of cancer, ocular neovascular disorders, chronic kidney diseases, and more. Despite their great importance, the mechanisms by which Robo receptors switch from their "off" to "on" states remain obscure. One possibility involves a monomer-to-dimer or dimer-to-monomer transition that facilitates the recruitment and activation of enzymatic effectors to instigate intracellular signaling...
October 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28993814/a-dopamine-receptor-genetic-variant-enhances-perceptual-speed-in-cognitive-healthy-subjects
#18
S Barral, C Habeck, E Gazes, P L De Jager, D A Bennett, Y Stern
Cognition is under strong genetic control, yet the specific genes are unknown. To investigate genetic influences on specific cognitive domains, 153 cognitive healthy subjects of European ancestry from the Reference Abilities Study (RANN) were genotyped for 1,160 variants within 446 neuropsychiatric genes. Adjusted linear regression models evaluated the association between the genetic variants and four reference abilities, which capture variance in age-related cognitive function (Vocabulary, Episodic Memory, Perceptual Speed, and Reasoning)...
June 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28975698/dopamine-d4-receptor-activation-restores-ca1-ltp-in-hippocampal-slices-from-aged-mice
#19
Fangli Guo, Jianhua Zhao, Dandan Zhao, Jiangang Wang, Xiaofang Wang, Zhiwei Feng, Martin Vreugdenhil, Chengbiao Lu
Normal aging is characterized with a decline in hippocampal memory functions that is associated with changes in long-term potentiation (LTP) of the CA3-to-CA1 synapse. Age-related deficit of the dopaminergic system may contribute to impairment of CA1 LTP. Here we assessed how the modulation of CA1 LTP by dopamine is affected by aging and how it is dependent on the Ca(2+) source. In slices from adult mice, the initial slope of the field potential showed strong LTP, but in slices from aged mice LTP was impaired...
December 2017: Aging Cell
https://www.readbyqxmd.com/read/28948862/interaction-between-central-gabaa-receptor-and-dopaminergic-system-on-food-intake-in-neonatal-chicks-role-of-d1-and-gabaa-receptors
#20
Mona Hashemzadeh, Morteza Zendehdel, Vahab Babapour, Negar Panahi
OBJECTIVE: The present study designed to examine the role of central GABAA receptors and dopaminergic system on feeding behavior in neonatal layer-type chicken. METHODS: In this study, 6 experiments designed, each with 4 treatment groups (n = 44 in each experiment). In experiment 1, four groups of FD3 chicks received a dose of either the ICV injection of (A) control solution, (B) L-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), (C) Gaboxadol (GABAA receptor agonist, 0...
September 26, 2017: International Journal of Neuroscience
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