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dopamine 2 receptor

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https://www.readbyqxmd.com/read/29908239/the-psychostimulant-%C3%A2-cis-4-4-dimethylaminorex-4-4-dmar-interacts-with-human-plasmalemmal-and-vesicular-monoamine-transporters
#1
Julian Maier, Felix P Mayer, Dino Luethi, Marion Holy, Kathrin Jäntsch, Harald Reither, Lena Hirtler, Marius C Hoener, Matthias E Liechti, Christian Pifl, Simon D Brandt, Harald H Sitte
(±)-cis-4,4'-Dimethylaminorex (4,4'-DMAR) is a new psychoactive substance (NPS) that has been associated with 31 fatalities and other adverse events in Europe between June 2013 and February 2014. We used in vitro uptake inhibition and transporter release assays to determine the effects of 4,4'-DMAR on human high-affinity transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT). In addition, we assessed its binding affinities to monoamine receptors and transporters. Furthermore, we investigated the interaction of 4,4'-DMAR with the vesicular monoamine transporter 2 (VMAT2) in rat phaeochromocytoma (PC12) cells and synaptic vesicles prepared from human striatum...
June 13, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29907842/reward-representing-d1-type-neurons-in-the-medial-shell-of-the-accumbens-nucleus-regulate-palatable-food-intake
#2
Máté Durst, Katalin Könczöl, Tamás Balázsa, Mark D Eyre, Zsuzsanna E Tóth
BACKGROUND/OBJECTIVES: Dysfunction in reward-related aspects of feeding, and consequent overeating in humans, is a major contributor to obesity. Intrauterine undernutrition and overnutrition are among the predisposing factors, but the exact mechanism of how overeating develops is still unclear. Consummatory behavior is regulated by the medial shell (mSh) of the accumbens nucleus (Nac) through direct connections with the rostral part of the lateral hypothalamic area (LHA). Our aim was to investigate whether an altered Nac-LHA circuit may underlie hyperphagic behavior...
June 15, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29907594/repositioning-dopamine-d2-receptor-agonist-bromocriptine-to-enhance-docetaxel-chemotherapy-and-treat-bone-metastatic-prostate-cancer
#3
Yang Yang, Kenza Mamouni, Xin Li, Yanhua Chen, Sravan Kavuri, Yuhong Du, Haian Fu, Omer Kucuk, Daqing Wu
Docetaxel resistance remains a major obstacle in the treatment of prostate cancer (PCa) bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of PCa in preclinical models. DRD2 is ubiquitously expressed in PCa cell lines, and DRD2 is significantly reduced in PCa tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in PCa cells, but effectively induces cell cycle arrest...
June 15, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29905970/neurexin-superfamily-cell-membrane-receptor-contactin-associated-protein-like-4-cntnap4-is-involved-in-neural-egfl-like-1-nell-1-responsive-osteogenesis
#4
Chenshuang Li, Zhong Zheng, Pin Ha, Xiaoyan Chen, Wenlu Jiang, Shan Sun, Feng Chen, Greg Asatrian, Emily A Berthiaume, Jong Kil Kim, Eric C Chen, Shen Pang, Xinli Zhang, Kang Ting, Chia Soo
Contactin-associated protein-like 4 (Cntnap4) is a member of the neurexin superfamily of transmembrane molecules that have critical functions in neuronal cell communication. Cntnap4 knockout mice display decreased presynaptic gamma-aminobutyric acid (GABA) and increased dopamine release that is associated with severe, highly penetrant, repetitive, and perseverative movements commonly found in human autism spectrum disorder patients. However, no known function of Cntnap4 has been revealed besides the nervous system...
June 15, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29905488/effects-of-interaction-between-drd4-methylation-and-prenatal-maternal-stress-on-methylphenidate-induced-changes-in-continuous-performance-test-performance-in-youth-with-attention-deficit-hyperactivity-disorder
#5
Johanna Inhyang Kim, Jae-Won Kim, Inkyung Shin, Bung-Nyun Kim
OBJECTIVES: Environmental factors may interact with genetic factors via the epigenetic process, and this interaction can contribute to inter-individual variability in the treatment response. The purpose of this study was to investigate the interaction effects between dopamine receptor D4 (DRD4) methylation and prenatal maternal stress on the methylphenidate (MPH) response of youth with attention-deficit/hyperactivity disorder (ADHD). METHODS: This study was an 8-week open-label trial of MPH that included 74 ADHD youth...
June 15, 2018: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/29900533/relations-between-early-maternal-sensitivity-and-toddler-self-regulation-exploring-variation-by-oxytocin-and-dopamine-d2-receptor-genes
#6
Mairin E Augustine, Esther M Leerkes, Andrew Smolen, Susan D Calkins
Gene-by-environment interactions between maternal sensitivity during infancy and child oxytocin receptor gene (OXTR rs53576) and D2 dopamine receptor gene (DRD2 TaqIA, rs1822497) genotypes were explored as predictors of toddlers' well-regulated behavioral and physiological responses to maternal compliance demands. Maternal sensitivity was assessed across a range of mother-child interactions when children were 6 months and 1 year of age (N = 186), and toddler self-regulatory responses were assessed through compliance and vagal withdrawal during a toy clean-up task when children were 2 years of age...
June 13, 2018: Developmental Psychobiology
https://www.readbyqxmd.com/read/29897417/prefrontal-d1-dopamine-receptor-neurons-and-delta-resonance-in-interval-timing
#7
Young-Cho Kim, Nandakumar S Narayanan
Considerable evidence has shown that prefrontal neurons expressing D1-type dopamine receptors (D1DRs) are critical for working memory, flexibility, and timing. This line of work predicts that frontal neurons expressing D1DRs mediate cognitive processing. During timing tasks, one form this cognitive processing might take is time-dependent ramping activity-monotonic changes in firing rate over time. Thus, we hypothesized the prefrontal D1DR+ neurons would strongly exhibit time-dependent ramping during interval timing...
June 12, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29896154/basis-and-design-of-a-randomized-clinical-trial-to-evaluate-the-effect-of-levosulpiride-on-retinal-alterations-in-patients-with-diabetic-retinopathy-and-diabetic-macular-edema
#8
Ma Ludivina Robles-Osorio, Renata García-Franco, Carlos D Núñez-Amaro, Ximena Mira-Lorenzo, Paulina Ramírez-Neria, Wendy Hernández, Ellery López-Star, Thomas Bertsch, Gonzalo Martínez de la Escalera, Jakob Triebel, Carmen Clapp
Background: Diabetic retinopathy (DR) and diabetic macular edema (DME) are potentially blinding, microvascular retinal diseases in people with diabetes mellitus. Preclinical studies support a protective role of the hormone prolactin (PRL) due to its ocular incorporation and conversion to vasoinhibins, a family of PRL fragments that inhibit ischemia-induced retinal angiogenesis and diabetes-derived retinal vasopermeability. Here, we describe the protocol of an ongoing clinical trial investigating a new therapy for DR and DME based on elevating the circulating levels of PRL with the prokinetic, dopamine D2 receptor blocker, levosulpiride...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29892233/-in-vitro-neurochemical-assessment-of-methylphenidate-and-its-legal-high-analogs-3-4-ctmp-and-ethylphenidate-in-rat-nucleus-accumbens-and-bed-nucleus-of-the-stria-terminalis
#9
Colin Davidson, Christopher A R Raby, Vincenzo Barrese, John Ramsey
3,4-dichloromethylphenidate (3,4-CTMP) and ethylphenidate are new psychoactive substances and analogs of the attention deficit medication methylphenidate. Both drugs have been reported on online user fora to induce effects similar to cocaine. In the UK, 3,4-CTMP appeared on the drug market in 2013 and ethylphenidate has been sold since 2010. We aimed to explore the neurochemical effects of these drugs on brain dopamine and noradrenaline efflux. 3,4-CTMP and ethylphenidate, purchased from online vendors, were analyzed using gas chromatography and mass spectroscopy to confirm their identity...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29890071/subtle-modifications-to-the-indole-2-carboxamide-motif-of-the-negative-allosteric-modulator-n-trans-4-2-7-cyano-3-4-dihydroisoquinolin-2-1-h-yl-ethyl-cyclohexyl-1-h-indole-2-carboxamide-sb269652-yield-dramatic-changes-in-pharmacological-activity-at-the-dopamine
#10
Anitha Kopinathan, Christopher J Draper-Joyce, Monika Szabo, Peter J Scammells, J Robert Lane, Ben Capuano
SB269652 (1) is a negative allosteric modulator of the dopamine D2 receptor. Herein, we present the design, synthesis and pharmacological evaluation of 'second generation' analogues of 1 whereby subtle modifications to the indole-2-carboxamide motif confer dramatic changes in functional affinity (5000-fold increase), cooperativity (100-fold increase), and a novel action to modulate dopamine efficacy. Thus structural changes to this region of (1) allow the generation of a novel set of analogues with distinct pharmacological properties...
June 11, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29885849/ppar%C3%A3-%C3%AE-agonist-alleviates-nlrp3-inflammasome-mediated-neuroinflammation-in-the-mptp-mouse-model-of-parkinson-s-disease
#11
Linfang Chen, Liujun Xue, Jinlong Zheng, Xiangyang Tian, Yingdong Zhang, Qiang Tong
Recent studies have indicated that peroxisome proliferator-activated receptor β/δ (PPARß/δ) agonists exert neuroprotective effects in the model of Parkinson's disease (PD). Furthermore, PPARß/δ agonists have been shown to have potential anti-inflammatory activity, but the underlying mechanisms remain obscure. Emerging evidence indicates that the nucleotide-binding domain and leucine-rich-repeat-protein 3 (NLRP3) inflammasome-mediated neuroinflammation plays a crucial role in the pathogenesis of PD. In the present study we investigate whether PPARß/δ agonists alleviate NLRP3-mediated neuroinflammation in the 1- methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of PD...
June 7, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29885323/molecular-mechanisms-involved-in-epidermal-growth-factor-receptor-mediated-inhibition-of-dopamine-d-3-receptor-signaling
#12
Ningning Sun, Xiaowei Zhang, Shuohan Guo, Hang Thi Le, Xiaohan Zhang, Kyeong-Man Kim
The phenomenon wherein the signaling by a given receptor is regulated by a different class of receptors is termed transactivation or crosstalk. Crosstalk between receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs) is highly diverse and has unique functional implications because of the distinct structural features of the receptors and the signaling pathways involved. The present study used the epidermal growth factor receptor (EGFR) and dopamine D3 receptor (D3 R), which are both associated with schizophrenia, as the model system to study crosstalk between RTKs and GPCRs...
June 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29884934/deorphanization-of-olfactory-trace-amine-associated-receptors
#13
Qian Li
Olfaction is the primary sense used by most animals to perceive the external world. The mouse olfactory system is composed of several sensory structures, the largest of which is the main olfactory epithelium (MOE). Olfactory sensory neurons (OSNs) located within the MOE detect odors and pheromones using dedicated seven-transmembrane G protein-coupled receptors (GPCRs). Two families of GPCRs are expressed in the MOE and are conserved in humans and other vertebrates: odorant receptors (ORs) and trace amine-associated receptors (TAARs)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29883636/expression-of-dopamine-d2-and-d3-receptors-in-the-human-retina-revealed-by-positron-emission-tomography-and-targeted-mass-spectrometry
#14
Fernando Caravaggio, Enzo Scifo, Etienne L Sibille, Sergio E Hernandez-Da Mota, Philip Gerretsen, Gary Remington, Ariel Graff-Guerrero
Dopamine D2 receptors (D2 R) are expressed in the human retina and play an important role in the modulation of neural responses to light-adaptation. However, it is unknown whether dopamine D3 receptors (D3 R) are expressed in the human retina. Using positron emission tomography (PET), we have observed significant uptake of the D3 R-preferring agonist radiotracer [11 C]-(+)-PHNO into the retina of humans in vivo. This led us to examine whether [11 C]-(+)-PHNO binding in the retina was quantifiable using reference tissue methods and if D3 R are expressed in human post-mortem retinal tissue...
June 5, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29882218/methylene-blue-protects-dopaminergic-neurons-against-mptp-induced-neurotoxicity-by-upregulating-brain-derived-neurotrophic-factor
#15
Sunil Bhurtel, Nikita Katila, Sabita Neupane, Sunil Srivastav, Pil-Hoon Park, Dong-Young Choi
The relatively old, yet clinically used, drug methylene blue (MB) is known to possess neuroprotective properties by reducing aggregated proteins, augmenting the antioxidant response, and enhancing mitochondrial function and survival in various models of neurodegenerative diseases. In this study, we aimed to examine the effects of MB in Parkinson's disease (PD) in vivo and in vitro models by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP+ ) with a focus on possible effects on induction of neurotrophic factors...
June 7, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29880884/cocaine-engages-a-non-canonical-dopamine-independent-mechanism-that-controls-neuronal-excitability-in-the-nucleus-accumbens
#16
Ilse Delint-Ramirez, Francisco Garcia-Oscos, Amir Segev, Saïd Kourrich
Drug-induced enhanced dopamine (DA) signaling in the brain is a canonical mechanism that initiates addiction processes. However, indirect evidence suggests that cocaine also triggers non-canonical, DA-independent, mechanisms that contribute to behavioral responses to cocaine, including psychomotor sensitization and cocaine self-administration. Identifying these mechanisms and determining how they are initiated is fundamental to further our understanding of addiction processes. Using physiologically relevant in vitro tractable models, we found that cocaine-induced hypoactivity of nucleus accumbens shell (NAcSh) medium spiny neurons (MSNs), one hallmark of cocaine addiction, is independent of DA signaling...
June 7, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29878268/the-protein-status-of-rats-affects-the-rewarding-value-of-meals-due-to-their-protein-content
#17
Catherine Chaumontet, Isidra Recio, Gilles Fromentin, Simon Benoit, Julien Piedcoq, Nicolas Darcel, Daniel Tomé
Background: Protein status is controlled by the brain, which modulates feeding behavior to prevent protein deficiency. Objective: This study tested in rats whether protein status modulates feeding behavior through brain reward pathways. Methods: Experiments were conducted in male Wistar rats (mean ± SD weight; 230 ± 16 g). In experiment 1, rats adapted for 2 wk to a low-protein (LP; 6% of energy) or a normal-protein (NP; 14% of energy) diet were offered a choice between 3 cups containing high-protein (HP; 50% of energy), NP, or LP feed; their intake was measured for 24 h...
June 1, 2018: Journal of Nutrition
https://www.readbyqxmd.com/read/29876878/role-of-the-prefrontal-cortex-in-pain-processing
#18
REVIEW
Wei-Yi Ong, Christian S Stohler, Deron R Herr
The prefrontal cortex (PFC) is not only important in executive functions, but also pain processing. The latter is dependent on its connections to other areas of the cerebral neocortex, hippocampus, periaqueductal gray (PAG), thalamus, amygdala, and basal nuclei. Changes in neurotransmitters, gene expression, glial cells, and neuroinflammation occur in the PFC during acute and chronic pain, that result in alterations to its structure, activity, and connectivity. The medial PFC (mPFC) could serve dual, opposing roles in pain: (1) it mediates antinociceptive effects, due to its connections with other cortical areas, and as the main source of cortical afferents to the PAG for modulation of pain...
June 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29870053/prenatal-exposure-to-alcohol-induces-functional-and-structural-plasticity-in-dopamine-d1-receptor-expressing-neurons-of-the-dorsomedial-striatum
#19
Yifeng Cheng, Xuehua Wang, Xiaoyan Wei, Xueyi Xie, Sebastian Melo, Rajesh C Miranda, Jun Wang
BACKGROUND: Prenatal alcohol exposure (PAE) is a leading cause of hyperactivity in children. Excitation of dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) of the dorsomedial striatum (DMS), a brain region that controls voluntary behavior, is known to induce hyperactivity in mice. We therefore hypothesized that PAE-linked hyperactivity was due to persistently altered glutamatergic activity in DMS D1-MSNs. METHODS: Female Ai14 tdTomato-reporter mice were given access to alcohol in an intermittent-access, 2-bottle choice paradigm before pregnancy, and following mating with male D1-Cre mice, through the pregnancy period, and until postnatal day (P) 10...
June 5, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29864631/protein-expression-of-somatostatin-receptor-2-somatostatin-receptor-5-and-dopamine-d2-receptor-in-normal-pituitary-gland-and-acth-secreting-pituitary-adenoma-in-dogs
#20
Asaka Sato, Yasushi Hara
PURPOSE: To evaluate the protein expression of somatostatin receptor (SSTR) 2, SSTR5 and dopamine D2 receptor (DA2R)-targets of somatostatin analogs and dopamine agonists-in normal canine pituitary and canine adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. METHODS: Six normal canine pituitary glands and 14 canine ACTH-secreting pituitary adenoma cases were included in this study. The protein expression of SSTR2, SSTR5 and DA2R was determined by double-label immunofluorescence staining of these receptors and ACTH...
May 4, 2018: Research in Veterinary Science
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