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https://www.readbyqxmd.com/read/29703992/dynamic-tuneable-g-protein-coupled-receptor-monomer-dimer-populations
#1
Patricia M Dijkman, Oliver K Castell, Alan D Goddard, Juan C Munoz-Garcia, Chris de Graaf, Mark I Wallace, Anthony Watts
G protein-coupled receptors (GPCRs) are the largest class of membrane receptors, playing a key role in the regulation of processes as varied as neurotransmission and immune response. Evidence for GPCR oligomerisation has been accumulating that challenges the idea that GPCRs function solely as monomeric receptors; however, GPCR oligomerisation remains controversial primarily due to the difficulties in comparing evidence from very different types of structural and dynamic data. Using a combination of single-molecule and ensemble FRET, double electron-electron resonance spectroscopy, and simulations, we show that dimerisation of the GPCR neurotensin receptor 1 is regulated by receptor density and is dynamically tuneable over the physiological range...
April 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/29690638/neurotensin-is-a-lipid-induced-gastrointestinal-peptide-associated-with-visceral-adipose-tissue-inflammation-in-obesity
#2
Ilaria Barchetta, Flavia Agata Cimini, Danila Capoccia, Laura Bertoccini, Valentina Ceccarelli, Caterina Chiappetta, Frida Leonetti, Claudio Di Cristofano, Gianfranco Silecchia, Marju Orho-Melander, Olle Melander, Maria Gisella Cavallo
Neurotensin (NT) is a 13-amino acid peptide localized in the neuroendocrine cells of the small intestine, which promotes fat absorption and fatty acids translocation in response to lipid ingestion. NT-knock-out mice fed with a high-fat diet are protected from obesity, fatty liver, and the development of insulin-resistance. In humans, higher plasma levels of pro-NT, which is the stable circulating precursor of NT, predict obesity, type 2 diabetes (T2D), and cardiovascular disease. In obesity, the presence of visceral adipose tissue (VAT) inflammation leads to unfavorable metabolic outcomes and is associated with the development of T2D and non-alcoholic fatty liver disease (NAFLD)...
April 23, 2018: Nutrients
https://www.readbyqxmd.com/read/29680483/iontophoresis-stimulated-silk-fibroin-films-as-a-peptide-delivery-system-for-wound-healing
#3
Camila Nunes Lemos, Camila Cubayachi, Karina Dias, Jacqueline Nakau Mendonça, Norberto Peporine Lopes, Niege Araçari Jacometti Cardoso Furtado, Renata F V Lopez
Silk fibroin (SF) films containing a peptide, neurotensin (NT), stimulated by iontophoresis were developed with an aim to modulate the inflammatory process and prevent the growth of microorganisms typical of wounds. NT-loaded SF films composition shows predominance of β-sheet structures that conferred adequate mechanical properties, transparency, moderate roughness and low swelling index to fibroin films. Infrared spectroscopy and thermal analysis suggested the presence of non-covalent interactions between NT and fibroin...
April 19, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29656109/bile-acids-are-important-direct-and-indirect-regulators-of-the-secretion-of-appetite-and-metabolism-regulating-hormones-from-the-gut-and-pancreas
#4
Rune E Kuhre, Nicolai J Wewer Albrechtsen, Olav Larsen, Sara L Jepsen, Emilie Balk-Møller, Daniel B Andersen, Carolyn F Deacon, Kristina Schoonjans, Frank Reimann, Fiona M Gribble, Reidar Albrechtsen, Bolette Hartmann, Mette M Rosenkilde, Jens J Holst
OBJECTIVE: Bile acids (BAs) facilitate fat absorption and may play a role in glucose and metabolism regulation, stimulating the secretion of gut hormones. The relative importance and mechanisms involved in BA-stimulated secretion of appetite and metabolism regulating hormones from the gut and pancreas is not well described and was the purpose of this study. METHODS: The effects of bile acids on the secretion of gut and pancreatic hormones was studied in rats and compared to the most well described nutritional secretagogue: glucose...
March 17, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29596791/optimization-and-13-ch-3-methionine-labeling-of-a-signaling-competent-neurotensin-receptor-1-variant-for-nmr-studies
#5
Fabian Bumbak, Alastair C Keen, Natalie J Gunn, Paul R Gooley, Ross A D Bathgate, Daniel J Scott
Neurotensin is a 13-residue peptide that acts as a neuromodulator of classical neurotransmitters such as dopamine and glutamate in the mammalian central nervous system, mainly by activating the G protein-coupled receptor (GPCR), neurotensin receptor 1 (NTS1 ). Agonist binding to GPCRs shifts the conformational equilibrium of the transmembrane helices towards distinct, thermodynamically favorable conformations that favor effector protein interactions and promotes cell signaling. The introduction of site specific labels for NMR spectroscopy has proven useful for investigating this dynamic process, but the low expression levels and poor stability of GPCRs is a hindrance to solution NMR experiments...
March 26, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29590379/increased-plasma-proneurotensin-levels-identify-nafld-in-adults-with-and-without-type-2-diabetes
#6
Ilaria Barchetta, Flavia Agata Cimini, Frida Leonetti, Danila Capoccia, Claudio Di Cristofano, Gianfranco Silecchia, Marju Orho-Melander, Olle Melander, Maria Gisella Cavallo
Context: Neurotensin (NT) is an intestinal peptide released by fat ingestion and promoting lipids absorption; higher circulating NT levels associate with type 2 diabetes (T2D), obesity and cardiovascular disease. Whether NT is related to non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) has not been fully investigated. Objective: To study the relationship between plasma proneurotensin1-117 (pro-NT), a stable fragment of the NT precursor hormone, and the presence/severity of NAFLD/NASH and to unravel correlates of increased pro-NT levels...
March 23, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29569407/neurotensin-and-neurotensin-receptor-1-mrna-expression-in-song-control-regions-changes-during-development-in-male-zebra-finches
#7
Devin P Merullo, Chinweike N Asogwa, Miguel Sanchez-Valpuesta, Shin Hayase, Bikash R Pattnaik, Kazuhiro Wada, Lauren V Riters
Learned vocalizations are important for communication in some vertebrate taxa. The neural circuitry for the learning and production of vocalizations is well-known in songbirds, many of which learn songs initially during a critical period early in life. Dopamine is essential for motor learning, including song learning, and dopamine-related measures change throughout development in song-control regions such as HVC, the lateral magnocellular nucleus of the anterior nidopallium (LMAN), Area X, and the robust nucleus of the arcopallium (RA)...
March 22, 2018: Developmental Neurobiology
https://www.readbyqxmd.com/read/29546332/proneurotensin-predicts-cardiovascular-disease-in-an-elderly-population
#8
Ayesha Fawad, Andreas Bergmann, Joachim Struck, Peter M Nilsson, Marju Orho-Melander, Olle Melander
Context: The gut hormone neurotensin promotes fat absorption, diet-induced weight gain and liver steatosis. Its stable precursor-hormone fragment "proneurotensin" predicts cardiometabolic disease in middle-aged populations, especially in women. Objective: To test if proneurotensin predicts cardiovascular disease (CVD) and diabetes development in an elderly population and whether there are gender differences in this respect. Design, Setting and Participants: Fasting proneurotensin was measured in plasma from 4804 participants (mean age 69±6 years) of the Malmö Preventive Project (MPP) and subjects were followed up for development of CVD and diabetes during 5...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29545146/reduced-learning-and-memory-performances-in-high-fat-treated-hamsters-related-to-brain-neurotensin-receptor1-expression-variations
#9
Gilda Fazzari, Merylin Zizza, Anna Di Vito, Raffaella Alò, Maria Mele, Rosalinda Bruno, Barni Tullio, Rosa Maria Facciolo, Canonaco Marcello
Recent indications are suggesting that high fat and sugar-enriched foods do not only evoke harmful physiological conditions, but they also endure evident structural alterations in cerebral regions controlling cognitive and feeding behaviors. Food consumption plus neuronal energy regulatory mechanisms seem to constitute a complex system assuring that food calories do not exceed body requirements. At the same time obesogenic-related properties of limbic feeding stations like the hypothalamus (HTH), hippocampus (HIP) and amygdala (AMY) tend to control eating habits through the interaction of distinct neuropeptides...
March 12, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29541365/in-search-of-the-optimal-macrocyclization-site-for-neurotensin
#10
Marc Sousbie, Élie Besserer-Offroy, Rebecca L Brouillette, Jean-Michel Longpré, Richard Leduc, Philippe Sarret, Éric Marsault
Neurotensin exerts potent analgesic effects following activation of its cognate GPCRs. In this study, we describe a systematic exploration, using structure-based design, of conformationally constraining neurotensin (8-13) with the help of macrocyclization and the resulting impacts on binding affinity, signaling, and proteolytic stability. This exploratory study led to a macrocyclic scaffold with submicromolar binding affinity, agonist activity, and greatly improved plasma stability.
March 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29530527/stimulation-of-white-adipose-tissue-lipolysis-by-xenin-a-neurotensin-related-peptide
#11
Sharma Bhavya, Pei San Lew, Tooru M Mizuno
Xenin is a gastrointestinal hormone that belongs to the neurotensin family. Central administration of xenin to obese mice reduces food intake and body weight gain and causes alterations in the expression of lipid metabolism-related genes and proteins in white adipose tissue (WAT). However, it has not been tested whether or not xenin directly acts on adipose tissue and alters lipid metabolism. The present study was performed to address this possibility by examining the effect of xenin treatment on the levels of glycerol and free fatty acids (FFA) and expression levels of lipolysis marker proteins ex vivo in cultured mouse WAT...
March 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29527569/collateral-projections-innervate-the-mammillary-bodies-and-retrosplenial-cortex-a-new-category-of-hippocampal-cells
#12
Lisa Kinnavane, Seralynne D Vann, Andrew J D Nelson, Shane M O'Mara, John P Aggleton
To understand the hippocampus, it is necessary to understand the subiculum. Unlike other hippocampal subfields, the subiculum projects to almost all distal hippocampal targets, highlighting its critical importance for external networks. The present studies, in male rats and mice, reveal a new category of dorsal subiculum neurons that innervate both the mammillary bodies (MBs) and the retrosplenial cortex (RSP). These bifurcating neurons comprise almost half of the hippocampal cells that project to RSP. The termination of these numerous collateral projections was visualized within the medial mammillary nucleus and the granular RSP (area 29)...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29517633/potential-prediction-of-acute-biliary-pancreatitis-outcome-on-admission
#13
Angeliki Papapanagiotou, George Sgourakis, Stella Peristeraki, Dimitris Raptis, Kyriakos Karkoulias, Stergios Tezas, Panna Patel, Athanasios G Papavassiliou
OBJECTIVES: This pilot study aimed to determine the feasibility of serum values of osteonectin, adiponectin, transforming growth factor beta 1, and neurotensin being used in clinical practice to predict the severity of acute pancreatitis. METHODS: Blood samples were collected from 45 consecutive newly diagnosed acute pancreatitis patients and 30 matched healthy controls. The 2 groups were matched according to age, sex, weight, height, diabetes, smoking, and alcohol consumption...
April 2018: Pancreas
https://www.readbyqxmd.com/read/29516445/immunohistochemical-mapping-of-neurotensin-in-the-alpaca-diencephalon
#14
Manuel Lisardo Sánchez, Arturo Mangas, Luis Enrique Medina, Luis Angel Aguilar, Zaida Díaz-Cabiale, José Angel Narváez, Rafael Coveñas
INTRODUCTION: The distribution of the immunoreactive cell bodies and fibers containing neurotensin in the alpaca diencephalon was determined by an immunohistochemical technique. MATERIAL AND METHODS: The study was carried out in four male alpacas that lived at sea level. Brains of deeply anesthetized animals were fixed by perfusion with 4% paraformaldehyde. Cryostat sections were stained by a standard immunohistochemical method. RESULTS: Cell bodies containing neurotensin were observed in the zona incerta and hypothalamus...
2018: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29478718/determination-of-neurotensin-projections-to-the-ventral-tegmental-area-in-mice
#15
Hillary L Woodworth, Juliette A Brown, Hannah M Batchelor, Raluca Bugescu, Gina M Leinninger
Pharmacologic treatment with the neuropeptide neurotensin (Nts) modifies motivated behaviors such as feeding, locomotor activity, and reproduction. Dopamine (DA) neurons of the ventral tegmental area (VTA) control these behaviors, and Nts directly modulates the activity of DA neurons via Nts receptor-1. While Nts sources to the VTA have been described in starlings and rats, the endogenous sources of Nts to the VTA of mice remain incompletely understood, impeding determination of which Nts circuits orchestrate specific behaviors in this model...
April 2018: Neuropeptides
https://www.readbyqxmd.com/read/29467963/new-extracellular-factors-in-glioblastoma-multiforme-development-neurotensin-growth-differentiation-factor-15-sphingosine-1-phosphate-and-cytomegalovirus-infection
#16
REVIEW
Jan Korbecki, Izabela Gutowska, Ireneusz Kojder, Dariusz Jeżewski, Marta Goschorska, Agnieszka Łukomska, Anna Lubkowska, Dariusz Chlubek, Irena Baranowska-Bosiacka
Recent years have seen considerable progress in understanding the biochemistry of cancer. For example, more significance is now assigned to the tumor microenvironment, especially with regard to intercellular signaling in the tumor niche which depends on many factors secreted by tumor cells. In addition, great progress has been made in understanding the influence of factors such as neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate (S1P), and infection with cytomegalovirus (CMV) on the 'hallmarks of cancer' in glioblastoma multiforme...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29464190/identification-of-neurotensin-receptor-expressing-cells-in-the-ventral-tegmental-area-across-the-lifespan
#17
Hillary L Woodworth, Patricia A Perez-Bonilla, Bethany G Beekly, Trevor J Lewis, Gina M Leinninger
Neurotensin (Nts) promotes activation of dopamine (DA) neurons in the ventral tegmental area (VTA) via incompletely understood mechanisms. Nts can signal via the G protein-coupled Nts receptors 1 and 2 (NtsR1 and NtsR2), but the lack of methods to detect NtsR1- and NtsR2-expressing cells has limited mechanistic understanding of Nts action. To overcome this challenge, we generated dual recombinase mice that express FlpO-dependent Cre recombinase in NtsR1 or NtsR2 cells. This strategy permitted temporal control over recombination, such that we could identify NtsR1- or NtsR2-expressing cells and determine whether their distributions differed between the developing and adult brain...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29462652/the-role-of-intraamygdaloid-neurotensin-and-dopamine-interaction-in-conditioned-place-preference
#18
K László, L Péczely, A Kovács, O Zagoracz, T Ollmann, E Kertes, V Kállai, B Csetényi, Z Karádi, L Lénárd
Tridecapeptide Neurotensin (NT) is widely distributed in the central nervous system where it acts as a neurotransmitter and neuromodulator. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. Our previous data showed that NT microinjected into the CeA has positive reinforcing properties. We supposed that these effects might be due to modulations of the mesolimbic dopamine system. The aim of our study was to examine in the CeA the possible effects of NT and dopamine interaction on reinforcement by conditioned place preference test...
May 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29445764/quantified-coexpression-analysis-of-central-amygdala-subpopulations
#19
Kenneth M McCullough, Filomene G Morrison, Jakob Hartmann, William A Carlezon, Kerry J Ressler
Molecular identification and characterization of fear controlling circuitries is a promising path towards developing targeted treatments of fear-related disorders. Three-color in situ hybridization analysis was used to determine whether somatostatin (SOM, Sst ), neurotensin (NTS, Nts ), corticotropin-releasing factor (CRF, Crf ), tachykinin 2 (TAC2, Tac2 ), protein kinase c-δ (PKC-δ, Prkcd ), and dopamine receptor 2 (DRD2, Drd2 ) mRNA colocalize in male mouse amygdala neurons. Expression and colocalization was examined across capsular (CeC), lateral (CeL), and medial (CeM) compartments of the central amygdala...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29417469/association-between-systemic-leptin-and-neurotensin-concentration-in-adult-individuals-with-and-without-type-2-diabetes-mellitus
#20
I Barchetta, G Ciccarelli, F A Cimini, V Ceccarelli, M Orho-Melander, O Melander, M G Cavallo
PURPOSE: Leptin is an adipokine which regulates appetite and energy balance through a mechanism partially mediated by neurotensin (NT) in central nervous system. Besides acting as a neurotransmitter, NT is expressed in human intestine where it promotes fat absorption and its circulating levels associate with obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease. Whether a relation exists between circulating leptin and NT levels has not been investigated yet. The aim of this study was to test the hypothesis of an association between plasma leptin and NT concentration in adults with or without T2DM...
February 7, 2018: Journal of Endocrinological Investigation
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