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https://www.readbyqxmd.com/read/28536844/evaluation-of-neurotensin-receptor-1-as-a-potential-imaging-target-in-pancreatic-ductal-adenocarcinoma
#1
Xiaoqin Yin, Mengzhe Wang, Hui Wang, Huaifu Deng, Tingting He, Yue Tan, Zehua Zhu, Zhanhong Wu, Shuo Hu, Zibo Li
Pancreatic cancer is one of the deadliest human malignancies and lack of effective diagnostic and therapeutic methods. Accumulating evidence suggests that the neurotensin (NT) and neurotensin receptors (NTRs) play key roles in pancreatic adenocarcinoma growth and survival. In this study, we not only evaluate the NTR1 expression in pancreatic cancer patient samples, but also explore the PET and fluorescence imaging of NTR1 expression in pancreatic cancer animal models. The NTR1 expression was evaluated by immunohistochemistry staining in clinical patient tissue samples with pancreatic ductal adenocarcinoma, insulinoma, and pancreatitis...
May 23, 2017: Amino Acids
https://www.readbyqxmd.com/read/28534946/differentiation-of-nestin%C3%A2-negative-human-hair-follicle-outer-root-sheath-cells-into-neurons-in%C3%A2-vitro
#2
Wei Wu, Xiao-Li Wu, Yu-Qing Ji, Zhen Gao
A specialized quiescent population of hair follicle stem cells, residing in the hair follicle outer root sheath cells (ORSCs), has previously demonstrated pluripotency for differentiation into neural stem cells (NSCs). A previous study indicated that nestin‑positive hair follicle ORSCs are able to differentiate into neurons. However, little has been reported on the isolation of nestin‑negative human ORSCs and whether they can successfully differentiate into neurons in vitro. In the present study, nestin‑positive ORSCs were significantly reduced with a prolonged incubation time in vitro...
May 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28522313/neurotensin-in-the-nucleus-accumbens-reverses-dopamine-supersensitivity-evoked-by-antipsychotic-treatment
#3
Alice Servonnet, Ellie-Anna Minogianis, Claude Bouchard, Anne-Marie Bédard, Daniel Lévesque, Pierre-Paul Rompré, Anne-Noël Samaha
Long-term exposure to antipsychotics like haloperidol can increase sensitivity to dopamine agonist stimulation. This could contribute to treatment failure and increase relapse to psychosis. Chronic antipsychotic treatment elevates neurotensin levels in the nucleus accumbens (NAc), where the neuropeptide modulates dopamine function by signalling through NTS1 receptors. We hypothesized that increasing neurotensin activity in the NAc attenuates the expression of antipsychotic-induced dopamine supersensitivity, which is indicated by a potentiated psychomotor response to amphetamine...
May 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28510609/spr-based-fragment-screening-with-neurotensin-receptor-1-generates-novel-small-molecule-ligands
#4
Sylwia Huber, Fabio Casagrande, Melanie N Hug, Lisha Wang, Philipp Heine, Lutz Kummer, Andreas Plückthun, Michael Hennig
The neurotensin receptor 1 represents an important drug target involved in various diseases of the central nervous system. So far, the full exploitation of potential therapeutic activities has been compromised by the lack of compounds with favorable physicochemical and pharmacokinetic properties which efficiently penetrate the blood-brain barrier. Recent progress in the generation of stabilized variants of solubilized neurotensin receptor 1 and its subsequent purification and successful structure determination presents a solid starting point to apply the approach of fragment-based screening to extend the chemical space of known neurotensin receptor 1 ligands...
2017: PloS One
https://www.readbyqxmd.com/read/28498396/diverse-expression-patterns-and-tumorigenic-role-of-neurotensin-signaling-components-in-colorectal-cancer-cells
#5
Ji Tae Kim, Heidi L Weiss, B Mark Evers
Colorectal cancer (CRC), which is one of the most common malignancies worldwide, results from an accumulation of genetic and epigenetic modifications including DNA methylation. Neurotensin (NTS), a hormone localized to the gut and central nervous system, mediates its physiological and pathological effects, including growth stimulation for a variety of cancers, through three distinct NTS receptors (NTSRs). Most NTS functions are mediated through the high-affinity receptor NTSR1, and expression of NTSR1 is increased in many cancers including CRC...
May 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28494471/inhibition-of-neurotensin-receptor-1-induces-intrinsic-apoptosis-via-let-7a-3p-bcl-w-axis-in-glioblastoma
#6
Zhen Dong, Qian Lei, Rui Yang, Shunqin Zhu, Xiao-Xue Ke, Liqun Yang, Hongjuan Cui, Liang Yi
Backgroud:Glioblastoma is a kind of highly malignant and aggressive tumours in the central nervous system. Previously, we found that neurotensin (NTS) and its high-affinity receptor 1 (NTSR1) had essential roles in cell proliferation and invasiveness of glioblastoma. Unexpectedly, cell death also appeared by inhibition of NTSR1 except for cell cycle arrest. However, the mechanisms were remained to be further explored. METHODS: Cells treated with SR48692, a selective antagonist of NTSR1, or NTSR1 shRNA were stained with Annexin V-FITC/PI and the apoptosis was assessed by flow cytometry...
May 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28476948/hierarchical-specification-of-pruriceptors-by-runt-domain-transcription-factor-runx1
#7
Lu Qi, Chengcheng Huang, Xiaohua Wu, Yeqi Tao, Jingjing Yan, Tianyong Shi, Cheng Cao, Lu Han, Mengsheng Qiu, Qiufu Ma, Zijing Liu, Yang Liu
The somatic sensory neurons in dorsal root ganglia (DRG) detect and transmit a diverse array of sensory modalities, such as pain, itch, cold, warm, touch and others. Recent genetic and single-cell RNA sequencing studies have revealed a group of DRG neurons that could be particularly relevant for acute and chronic itch information transmission. They express the natriuretic peptide type B (NPPB), as well as a cohort of receptors and neuropeptides that have been implicated in chronic itch manifestation, including the interleukin-31 receptor IL31ra and its co-receptor Osmr, the leuktriene receptor Cysltr2, somatostatin and neurotensin...
May 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28439124/characterisation-of-a-cell-free-synthesised-g-protein-coupled-receptor
#8
Patrick J Shilling, Fabian Bumbak, Daniel J Scott, Ross A D Bathgate, Paul R Gooley
G-protein coupled receptors are the largest family of integral membrane proteins found within the human genome. They function as receptors and modulators to a wide range of ligands and responses which are crucial for human health. GPCR study, specifically the investigation of structure and interaction to cognate ligands, is of high priority. Limitations for structural study can be traced in part, to obtaining suitable quantities of recombinant protein. We sought to address the limitations of traditional recombinant technologies by utilising an Escherichia coli based cell-free protein synthesis (CFPS) approach for production of a thermostable neurotensin receptor 1 (en2NTS1)...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28404689/methoxyluteolin-inhibits-neuropeptide-stimulated-tnf-cxcl8-and-vegf-release-via-mtor-activation-from-human-mast-cells
#9
Arti B Patel, Theoharis C Theoharides
Mast cells (MC) are critical for allergic reactions, but are also important in inflammatory processes. Stimulation by neuropeptides, such as substance P (SP) and neurotensin (NT) leads to release of pre-formed molecules stored in numerous MC secretory granules and newly-synthesized pro-inflammatory mediators, including tumor necrosis factor (TNF), interleukin 8 (CXCL8) and vascular endothelial growth factor (VEGF). Here, we investigate the role of mammalian target of rapamycin (mTOR) signaling in the stimulation of cultured human LAD2 MC by NT or SP, and the inhibitory effect of the natural flavonoids 3',4',5,7-tetrahydroxyflavone (luteolin) and its novel structural analog 3 ',4',5,7-tetramethoxyluteolin (methoxyluteolin)...
April 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28399479/changes-in-biochemical-markers-following-spinal-manipulation-a-systematic-review-and-meta-analysis
#10
REVIEW
Kesava Kovanur-Sampath, Ramakrishnan Mani, Jim Cotter, Angela Spontelli Gisselman, Steve Tumilty
The aim of this meta-analysis was to determine the effectiveness of spinal manipulation in influencing various biochemical markers in healthy and or symptomatic population. Electronic databases (n = 10) were searched (from inception till September 2016) and eight trials (325 participants) that met the inclusion criteria were included in the meta-analysis. Two authors independently extracted and assessed the risk of bias in included studies. Standardised mean differences for outcome measures were used to calculate effect sizes...
June 2017: Musculoskeletal Science & Practice
https://www.readbyqxmd.com/read/28377304/longitudinal-mri-evaluation-of-neuroprotective-effects-of-pharmacologically-induced-hypothermia-in-experimental-ischemic-stroke
#11
Silun Wang, Xiaohuan Gu, Ramesh Paudyal, Ling Wei, Thomas A Dix, Shan P Yu, Xiaodong Zhang
Pharmacologically induced hypothermia (PIH) shows promising neuroprotective effects after stroke insult. However, the dynamic evolution of stroke infarct during the hypothermic therapy has not been understood very well. In the present study, MRI was utilized to longitudinally characterize the infarct evolution in a mouse model of ischemic stroke treated by PIH using the neurotensin agonist HPI201. Adult male C57BL/6 mice underwent permanent occlusion of the right middle cerebra artery (MCA). Each animal received a vehicle or HPI201 intraperitoneal injection...
April 2, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28368584/use-of-molecular-modeling-to-design-selective-nts2-neurotensin-analogues
#12
Roberto Fanelli, Nicolas Floquet, Élie Besserer-Offroy, Bartholomé Delort, Mélanie Vivancos, Jean-Michel Longpré, Pedro Renault, Jean Martinez, Philippe Sarret, Florine Cavelier
Neurotensin exerts potent analgesia by acting at both NTS1 and NTS2 receptors, whereas NTS1 activation also results in other physiological effects such as hypotension and hypothermia. Here, we used molecular modeling approach to design highly selective NTS2 ligands by investigating the docking of novel NT[8-13] compounds at both NTS1 and NTS2 sites. Molecular dynamics simulations revealed an interaction of the Tyr(11) residue of NT[8-13] with an acidic residue (Glu(179)) located in the ECL2 of hNTS2 or with a basic residue (Arg(212)) at the same position in hNTS1...
April 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28360038/insulin-receptor-and-gpcr-crosstalk-stimulates-yap-via-pi3k-and-pkd-in-pancreatic-cancer-cells
#13
Fang Hao, Qinhong Xu, Yinglan Zhao, Jan V Stevens, Steven H Young, James Sinnett-Smith, Enrique Rozengurt
We examined the impact of crosstalk between the insulin receptor and G protein-coupled receptor (GPCR) signaling pathways on the regulation of Yes-associated protein (YAP) localization, phosphorylation, and transcriptional activity in the context of human pancreatic ductal adenocarcinoma (PDAC). Stimulation of PANC-1 or MiaPaCa-2 cells with insulin and neurotensin, a potent mitogenic combination of agonists for these cells, promoted striking YAP nuclear localization and decreased YAP phosphorylation at Ser(127) and Ser(397) Challenging PDAC cells with either insulin or neurotensin alone modestly induced the expression of YAP/TEAD-regulated genes, including connective tissue growth factor (CTGF), cysteine-rich angiogenic inducer 61 (CYR61), and CXCL5, whereas the combination of neurotensin and insulin induced a marked increase in the level of expression of these genes...
March 30, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28341345/the-signaling-signature-of-the-neurotensin-type-1-receptor-with-endogenous-ligands
#14
Élie Besserer-Offroy, Rebecca L Brouillette, Sandrine Lavenus, Ulrike Froehlich, Andrea Brumwell, Alexandre Murza, Jean-Michel Longpré, Éric Marsault, Michel Grandbois, Philippe Sarret, Richard Leduc
The human neurotensin 1 receptor (hNTS1) is a G protein-coupled receptor involved in many physiological functions, including analgesia, hypothermia, and hypotension. To gain a better understanding of which signaling pathways or combination of pathways are linked to NTS1 activation and function, we investigated the ability of activated hNTS1, which was stably expressed by CHO-K1 cells, to directly engage G proteins, activate second messenger cascades and recruit β-arrestins. Using BRET-based biosensors, we found that neurotensin (NT), NT(8-13) and neuromedin N (NN) activated the Gαq-, Gαi1-, GαoA-, and Gα13-protein signaling pathways as well as the recruitment of β-arrestins 1 and 2...
March 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28323938/loss-of-action-via-neurotensin-leptin-receptor-neurons-disrupts-leptin-and-ghrelin-mediated-control-of-energy-balance
#15
Juliette A Brown, Raluca Bugescu, Thomas Mayer, Adriana Gata-Garcia, Gizem Kurt, Hillary L Woodworth, Gina M Leinninger
The hormones ghrelin and leptin act via the lateral hypothalamic area (LHA) to modify energy balance but the underlying neural mechanisms remain unclear. We investigated how leptin and ghrelin engage LHA neurons to modify energy balance behaviors and whether there is any cross-talk between leptin and ghrelin-responsive circuits. We demonstrate that ghrelin activates LHA neurons expressing Hypocretin/Orexin (OX) to increase food intake. Leptin mediates anorectic actions via separate neurons expressing the long form of the leptin receptor (LepRb), many of which co-express the neuropeptide neurotensin (Nts); we refer to these as NtsLepRb neurons...
March 10, 2017: Endocrinology
https://www.readbyqxmd.com/read/28316623/a-review-of-the-role-of-neurotensin-and-its-receptors-in-colorectal-cancer
#16
REVIEW
Shengyang Qiu, Gianluca Pellino, Francesca Fiorentino, Shahnawaz Rasheed, Ara Darzi, Paris Tekkis, Christos Kontovounisios
Neurotensin (NTS) is a physiologically occurring hormone which affects the function of the gastrointestinal (GI) tract. In recent years, NTS, acting through its cellular receptors (NTSR), has been implicated in the carcinogenesis of several cancers. In colorectal cancer (CRC), a significant body of evidence, from in vitro and in vivo studies, is available which elucidates the molecular biology of NTS/NTSR signalling and the resultant growth of CRC cells. There is growing clinical data from human studies which corroborate the role NTS/NTSR plays in the development of human CRC...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28287433/theranostic-value-of-multimers-lessons-learned-from-trimerization-of-neurotensin-receptor-ligands-and-other-targeting-vectors
#17
Simone Maschauer, Jürgen Einsiedel, Dominik Reich, Harald Hübner, Peter Gmeiner, Hans-Jürgen Wester, Olaf Prante, Johannes Notni
Neurotensin receptor 1 (NTS1) is overexpressed on a variety of cancer entities; for example, prostate cancer, ductal pancreatic adenocarcinoma, and breast cancer. Therefore, it represents an interesting target for the diagnosis of these cancers types by positron emission tomography (PET) [...].
March 10, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28270751/understanding-the-role-of-gpcr-heteroreceptor-complexes-in-modulating-the-brain-networks-in-health-and-disease
#18
REVIEW
Dasiel O Borroto-Escuela, Jens Carlsson, Patricia Ambrogini, Manuel Narváez, Karolina Wydra, Alexander O Tarakanov, Xiang Li, Carmelo Millón, Luca Ferraro, Riccardo Cuppini, Sergio Tanganelli, Fang Liu, Malgorzata Filip, Zaida Diaz-Cabiale, Kjell Fuxe
The introduction of allosteric receptor-receptor interactions in G protein-coupled receptor (GPCR) heteroreceptor complexes of the central nervous system (CNS) gave a new dimension to brain integration and neuropsychopharmacology. The molecular basis of learning and memory was proposed to be based on the reorganization of the homo- and heteroreceptor complexes in the postjunctional membrane of synapses. Long-term memory may be created by the transformation of parts of the heteroreceptor complexes into unique transcription factors which can lead to the formation of specific adapter proteins...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28262417/cell-autonomous-excitation-of-midbrain-dopamine-neurons-by-endocannabinoid-dependent-lipid-signaling
#19
Stephanie C Gantz, Bruce P Bean
The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G-protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood. Using a preparation of dissociated mouse midbrain dopamine neurons to isolate effects on intrinsic excitability, we found that 100 nM 2-AG accelerated pacemaking and steepened the frequency-current relationship for burst-like firing...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28254866/proof-of-therapeutic-efficacy-of-a-novel-177-lu-labeled-neurotensin-receptor-1-antagonist-in-a-colon-carcinoma-xenograft-model
#20
Jörg Schulz, Martin Rohracker, Marvin Stiebler, Jürgen Goldschmidt, Franziska Stöber, Mercedes Noriega, Anette Pethe, Mathias Lukas, Frank Osterkamp, Ulrich Reineke, Aileen Höhne, Christiane Smerling, Holger Amthauer
Purpose: Increased expression of neurotensin receptor 1 (NTR1) has been shown in a large number of tumor entities like pancreatic or colon carcinoma. Hence, this receptor is a promising target for diagnostic imaging and radioligand therapy (RLT). Based on favorable biodistribution data of the NTR1-targeting agent (111)In-3BP 227, we investigated the therapeutic effect of its (177)Lu-labeled analog on the tumor growth of NTR1-positive HT29 colon carcinoma xenografts. Methods: 3BP 227 was labeled with (177)Lu...
March 2, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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