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https://www.readbyqxmd.com/read/27920206/activation-of-d2-dopamine-receptors-in-cd133-ve-cancer-stem-cells-in-non-small-cell-lung-carcinoma-inhibits-proliferation-clonogenic-ability-and-invasiveness-of-these-cells
#1
Soumyabrata Roy, Kai Lu, Mukti Kant Nayak, Avishek Bhuniya, Tithi Ghosh, Suman Kundu, Sarbari Ghosh, Rathindranath Baral, Partha Sarathi Dasgupta, Sujit Basu
Lung carcinoma is the leading cause of cancer-related death worldwide, and among this cancer, non-small cell lung carcinoma (NSCLC) comprises the majority of cases. Furthermore, recurrence and metastasis of NSCLC correlate well with CD133+ve tumor cells, a small population of tumor cells, which has been designated as cancer stem cells (CSC). We here for the first time have demonstrated high expression of D2 dopamine (DA) receptors in CD133+ve adenocarcinoma NSCLC cells. Also, activation of D2 DA receptors in these cells significantly inhibited their proliferation, clonogenic ability and invasiveness by suppressing extracellular-signal-regulated kinases 1/2 (ERK1/2) and AKT, downregulation of octamer-binding transcription factor 4 (Oct-4) expression and matrix metalloproteinase-9 (MMP-9) secretion by these cells...
December 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27914043/a-revisit-to-quantitative-pet-with-18-f-fdopa-of-high-specific-activity-using-a-high-resolution-condition-in-view-of-application-to-regenerative-therapy
#2
Go Akamatsu, Akihito Ohnishi, Kazuki Aita, Hiroyuki Nishida, Yasuhiko Ikari, Masahiro Sasaki, Nobuo Kohara, Michio Senda
OBJECTIVE: With the advent of regenerative/cell therapy for Parkinson's disease (PD), (18)F-FDOPA has drawn new attention as a biomarker of the therapeutic that cannot be evaluated with radiopharmaceuticals for dopamine transporter. Since most previous (18)F-FDOPA PET studies were carried out many years ago with a PET scanner of lower resolution and with (18)F-FDOPA of low specific activity synthesized from (18)F-F2, we used a newer PET/CT scanner with a high-resolution condition and (18)F-FDOPA synthesized from (18)F-F(-) to re-evaluate this technique on normal subjects and patients with PD, together with D2 receptor imaging with (11)C-raclopride (RAC)...
December 2, 2016: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#3
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27912066/cell-type-specific-optical-recording-of-membrane-voltage-dynamics-in-freely-moving-mice
#4
Jesse D Marshall, Jin Zhong Li, Yanping Zhang, Yiyang Gong, François St-Pierre, Michael Z Lin, Mark J Schnitzer
Electrophysiological field potential dynamics are of fundamental interest in basic and clinical neuroscience, but how specific cell types shape these dynamics in the live brain is poorly understood. To empower mechanistic studies, we created an optical technique, TEMPO, that records the aggregate trans-membrane voltage dynamics of genetically specified neurons in freely behaving mice. TEMPO has >10-fold greater sensitivity than prior fiber-optic techniques and attains the noise minimum set by quantum mechanical photon shot noise...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911814/distinct-cortical-and-striatal-actions-of-a-%C3%AE-arrestin-biased-dopamine-d2-receptor-ligand-reveal-unique-antipsychotic-like-properties
#5
Nikhil M Urs, Steven M Gee, Thomas F Pack, John D McCorvy, Tama Evron, Joshua C Snyder, Xiaobao Yang, Ramona M Rodriguiz, Emiliana Borrelli, William C Wetsel, Jian Jin, Bryan L Roth, Patricio O'Donnell, Marc G Caron
The current dopamine (DA) hypothesis of schizophrenia postulates striatal hyperdopaminergia and cortical hypodopaminergia. Although partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneously target both phenomena, they do not effectively improve cortical dysfunction. In this study, we investigate the potential for newly developed β-arrestin2 (βarr2)-biased D2R partial agonists to simultaneously target hyper- and hypodopaminergia. Using neuron-specific βarr2-KO mice, we show that the antipsychotic-like effects of a βarr2-biased D2R ligand are driven through both striatal antagonism and cortical agonism of D2R-βarr2 signaling...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909104/loss-of-plasticity-in-the-d2-accumbens-pallidal-pathway-promotes-cocaine-seeking
#6
J A Heinsbroek, D N Neuhofer, W C Griffin, G S Siegel, A-C Bobadilla, Y M Kupchik, P W Kalivas
Distinct populations of D1- and D2-dopamine receptor expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, while activity in D2-MSNs inhibits motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27903510/vitamin-d-supplementation-reduces-some-at1-aa-induced-downstream-targets-implicated-in-preeclampsia-including-hypertension
#7
Jessica L Faulkner, Lorena M Amaral, Denise C Cornelius, Mark W Cunningham, Tarek Ibrahim, Autumn Heep, Nathan Campbell, Nathan Usry, Kedra Wallace, Florian Herse, Ralf Dechend, Babbette D LaMarca
Autoantibodies to the angiotensin II (ANGII) type I receptor (AT1-AA) are associated with preeclampsia (PE). We found that Vitamin D supplementation reduced AT1-AA and blood pressure (MAP) in the RUPP rat model of PE. However, it was undetermined if the decrease in AT1-AA was the mechanism whereby Vitamin D lowered MAP or if it was through factors downstream of AT1-AA. Uterine artery resistance index, placental ET-1 and sFlt-1 are increased with AT1-AA induced hypertension and considered markers of PE in pregnant women...
November 30, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27902847/food-deprivation-facilitates-reinstatement-of-morphine-induced-conditioned-place-preference-role-of-intra-accumbal-dopamine-d2-like-receptors-in-associating-reinstatement-of-morphine-cpp-with-stress
#8
Fatemeh Sadeghzadeh, Vahab Babapour, Abbas Haghparast
The high rate of relapse to drug use is one of the main problems in the treatment of addiction. Stress plays the essential role in drug abuse and relapse; nevertheless, little is known about the mechanisms underlying stress and relapse. Accordingly, the effects of intra-accumbal administration of Sulpiride, as a dopamine D2-like receptor antagonist, on an ineffective morphine dose+food deprivation(FD)- and morphine priming-induced reinstatement of conditioned place preference (CPP). 104 adult male albino Wistar rats weighing 200-280g were bilaterally implanted by cannula into the nucleus accumbens (NAc)...
November 30, 2016: Synapse
https://www.readbyqxmd.com/read/27901585/a-review-of-positron-emission-tomography-studies-exploring-the-dopaminergic-system-in-substance-use-with-a-focus-on-tobacco-as-a-co-variate
#9
Thulasi Thiruchselvam, Saima Malik, Bernard Le Foll
With the evolving sensitivity of positron emission tomography (PET) and the emergence of novel radiotracers, greater insight has been gained into the dopaminergic system as it relates to substance use. In this review, we summarize PET investigations from the last ten years that explore the dopaminergic system in tobacco, alcohol, stimulant, opiates, and cannabis addiction. In light of the prevalence of substance co-use, this review will also explore the effect of tobacco and other substance abuse co-morbidity on the dopaminergic system across study samples in the reviewed literature...
November 30, 2016: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/27901175/adme-studies-and-preliminary-safety-pharmacology-of-ldt5-a-lead-compound-for-the-treatment-of-benign-prostatic-hyperplasia
#10
F Noël, J B Nascimento-Viana, L A S Romeiro, R O Silva, L F N Lemes, A S Oliveira, T B S Giorno, P D Fernandes, C L M Silva
This study aimed to estimate the absorption, distribution, metabolism and excretion (ADME) properties and safety of LDT5, a lead compound for oral treatment of benign prostatic hyperplasia that has previously been characterized as a multi-target antagonist of α1A-, α1D-adrenoceptors and 5-HT1A receptors. The preclinical characterization of this compound comprised the evaluation of its in vitro properties, including plasma, microsomal and hepatocytes stability, cytochrome P450 metabolism and inhibition, plasma protein binding, and permeability using MDCK-MDR1 cells...
2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/27899487/glomerular-endothelial-mitochondrial-dysfunction-is-essential-and-characteristic-of-diabetic-kidney-disease-susceptibility
#11
Ilse Daehn, Haiying Qi, Gabriella Casalena, Shaolin Shi, Liping Yu, Kerstin Ebefors, Yezhou Sun, Weijia Zhang, Vivette D'Agati, Detlef Schlondorff, Börje Haraldsson, Erwin Böttinger
The molecular signaling mechanisms between glomerular cell types during initiation/progression of diabetic kidney disease (DKD) remain poorly understood. We compared the early transcriptome profile between DKD resistant C57BL/6J (B6) and DKD susceptible DBA/2J (D2) glomeruli, and demonstrated a significant down regulation of essential mitochondrial genes in glomeruli from diabetic D2 mice, but not in B6 with comparable hyperglycemia. Diabetic D2 mice manifested increased mtDNA lesions (8-oxoG), exclusively localized to glomerular endothelial cells after 3 weeks of diabetes and these accumulated over time as well as increased urine secretion of 8-oxodG...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27898338/effect-of-pgd2-on-middle-meningeal-artery-and-mrna-expression-profile-of-l-pgd2-synthase-and-dp-receptors-in-trigeminovascular-system-and-other-pain-processing-structures-in-rat-brain
#12
Aysegül Sekeroglu, Julie Mie Jacobsen, Inger Jansen-Olesen, Saurabh Gupta, Majid Sheykhzade, Jes Olesen, Deepak K Bhatt
BACKGROUND: Prostaglandins (PGs), particularly prostaglandin D2 (PGD2), E2 (PGE2), and I2 (PGI2), are considered to play a role in migraine pain. In humans, infusion of PGD2 causes lesser headache as compared to infusion of PGE2 and PGI2. Follow-up studies in rats have shown that infusion of PGE2 and PGI2 dilate the middle meningeal artery (MMA), and mRNA for PGE2 and PGI2 receptors is present in rat trigeminovascular system (TVS) and in the brain structures associated with pain. In the present study, we have characterized the dilatory effect of PGD2 on rat MMA and studied the relative mRNA expression of PGD2 receptors and lipocalin-type of PGD2 synthase (L-PGDS)...
September 19, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27897674/dopamine-alters-the-fidelity-of-working-memory-representations-according-to-attentional-demands
#13
Sean James Fallon, Nahid Zokaei, Agnes Norbury, Sanjay G Manohar, Masud Husain
Capacity limitations in working memory (WM) necessitate the need to effectively control its contents. Here, we examined the effect of cabergoline, a dopamine D2 receptor agonist, on WM using a continuous report paradigm that allowed us to assess the fidelity with which items are stored. We assessed recall performance under three different gating conditions: remembering only one item, being cued to remember one target among distractors, and having to remember all items. Cabergoline had differential effects on recall performance according to whether distractors had to be ignored and whether mnemonic resources could be deployed exclusively to the target...
November 29, 2016: Journal of Cognitive Neuroscience
https://www.readbyqxmd.com/read/27896839/dopamine-elevates-and-lowers-astroglial-ca-2-through-distinct-pathways-depending-on-local-synaptic-circuitry
#14
Alistair Jennings, Olga Tyurikova, Lucie Bard, Kaiyu Zheng, Alexey Semyanov, Christian Henneberger, Dmitri A Rusakov
Whilst astrocytes in culture invariably respond to dopamine with cytosolic Ca(2+) rises, the dopamine sensitivity of astroglia in situ and its physiological roles remain unknown. To minimize effects of experimental manipulations on astroglial physiology, here we monitored Ca(2+) in cells connected via gap junctions to astrocytes loaded whole-cell with cytosolic indicators in area CA1 of acute hippocampal slices. Aiming at high sensitivity of [Ca(2+) ] measurements, we also employed life-time imaging of the Ca(2+) indicator Oregon Green BAPTA-1...
November 29, 2016: Glia
https://www.readbyqxmd.com/read/27896809/a2a-d2-receptor-receptor-interaction-modulates-gliotransmitter-release-from-striatal-astrocyte-processes
#15
Chiara Cervetto, Arianna Venturini, Mario Passalacqua, Diego Guidolin, Susanna Genedani, Kjell Fuxe, Dasiel O Borroto-Esquela, Pietro Cortelli, Amina Woods, Guido Maura, Manuela Marcoli, Luigi F Agnati
Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes...
November 5, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27893751/25-hydroxy-and-1%C3%AE-25-dihydroxycholecalciferol-have-greater-potencies-than-25-hydroxy-and-1%C3%AE-25-dihydroxyergocalciferol-in-modulating-cultured-human-and-mouse-osteoblast-activities
#16
Allahdad Zarei, Philippa A Hulley, Afsie Sabokbar, M Kassim Javaid, Alireza Morovat
Despite differences in the phamacokinetics of 25-hydroxycholecalciferol (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2) in man, the effects of these and their 1α-hydroxylated forms (1,25(OH)2D3 and 1,25(OH)2D2) on cellular activity of vitamin D-responsive cells have hardly been compared. We studied differences in the effects of these metabolites on cell number, gene transcription, protein expression and mineralisation of cultured human bone marrow-derived stromal cells (hBMSC) and rapidly mineralising mouse 2T3 osteoblasts...
2016: PloS One
https://www.readbyqxmd.com/read/27893588/suite-pet-ct-neuroimaging-for-the-diagnosis-of-parkinson-s-disease-statistical-parametric-mapping-analysis
#17
Ruimin Wang, Baixuan Xu, Zhe Guo, Tong Chen, Jinming Zhang, Yingmao Chen, Haiyan Zhu
OBJECTIVES: The aim of this study was to investigate the topographical distribution of dopamine transporter (DAT), dopamine D2 receptor, and glucose metabolism in Parkinson's disease (PD) using PET/computed tomography (CT) scanning and statistical parametric mapping (SPM) analysis. PARTICIPANTS AND METHODS: Seventy-four patients (58 PD patients and 16 normal controls) underwent DAT, D2 receptor, and glucose brain PET/CT scans using C-methyl-N-2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane (C-β-CFT), C-raclopride (C-RAC), and fluorine-18-fluorodeoxyglucose (F-FDG) radiotracers for the respective scans...
November 28, 2016: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/27891077/presynaptic-g-protein-coupled-receptors-gatekeepers-of-addiction
#18
REVIEW
Kari A Johnson, David M Lovinger
Drug abuse and addiction cause widespread social and public health problems, and the neurobiology underlying drug actions and drug use and abuse is an area of intensive research. Drugs of abuse alter synaptic transmission, and these actions contribute to acute intoxication as well as the chronic effects of abused substances. Transmission at most mammalian synapses involves neurotransmitter activation of two receptor subtypes, ligand-gated ion channels that mediate fast synaptic responses and G protein-coupled receptors (GPCRs) that have slower neuromodulatory actions...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27889491/pramipexole-enhances-disadvantageous-decision-making-lack-of-relation-to-changes-in-phasic-dopamine-release
#19
Romina Pes, Sean C Godar, Andrew T Fox, Lauren M Burgeno, Hunter J Strathman, David P Jarmolowicz, Paola Devoto, Beth Levant, Paul E Phillips, Stephen C Fowler, Marco Bortolato
Pramipexole (PPX) is a high-affinity D2-like dopamine receptor agonist, used in the treatment of Parkinson's disease (PD) and restless leg syndrome. Recent evidence indicates that PPX increases the risk of problem gambling and impulse-control disorders in vulnerable patients. Although the molecular bases of these complications remain unclear, several authors have theorized that PPX may increase risk propensity by activating presynaptic dopamine receptors in the mesolimbic system, resulting in the reduction of dopamine release in the nucleus accumbens (NAcc)...
November 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27886638/preliminary-evidence-that-negative-symptom-severity-relates-to-multilocus-genetic-profile-for-dopamine-signaling-capacity-and-d2-receptor-binding-in-healthy-controls-and-in-schizophrenia
#20
Sarah A Eisenstein, Ryan Bogdan, Ling Chen, Stephen M Moerlein, Kevin J Black, Joel S Perlmutter, Tamara Hershey, Deanna M Barch
Deficits in central, subcortical dopamine (DA) signaling may underlie negative symptom severity, particularly anhedonia, in healthy individuals and in schizophrenia. To investigate these relationships, we assessed negative symptoms with the Schedule for the Assessment of Negative Symptoms and the Brief Negative Symptom Scale (BNSS) and self-reported anhedonia with the Scales for Physical and Social Anhedonia (SPSA), Temporal Experience of Pleasure Scale, and Snaith-Hamilton Pleasure Scale in 36 healthy controls (HC), 27 siblings (SIB) of individuals with schizophrenia, and 66 individuals with schizophrenia or schizoaffective disorder (SCZ)...
November 17, 2016: Journal of Psychiatric Research
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