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neurotensin

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https://www.readbyqxmd.com/read/28202805/chenodeoxycholic-acid-stimulates-glucagon-like-peptide-1-secretion-in-patients-after-roux-en-y-gastric-bypass
#1
Signe Nielsen, Maria S Svane, Rune E Kuhre, Trine R Clausen, Viggo B Kristiansen, Jens F Rehfeld, Jens J Holst, Sten Madsbad, Kirstine N Bojsen-Moller
Postprandial secretion of glucagon-like peptide-1 (GLP-1) is enhanced after Roux-en-Y gastric bypass (RYGB), but the precise molecular mechanisms explaining this remain poorly understood. Plasma concentrations of bile acids (BAs) increase after RYGB, and BAs may act as molecular enhancers of GLP-1 secretion through activation of TGR5-receptors. We aimed to evaluate GLP-1 secretion after oral administration of the primary bile acid chenodeoxycholic acid (CDCA) and the secondary bile acid ursodeoxycholic acid (UDCA) (which are available for oral use) in RYGB-operated participants...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28194737/regio-selective-intramolecular-hydrogen-deuterium-exchange-in-gas-phase-electron-transfer-dissociation
#2
Yoshitomo Hamuro
Protein backbone amide hydrogen/deuterium exchange mass spectrometry (HDX-MS) typically utilizes enzymatic digestion after the exchange reaction and before MS analysis to improve data resolution. Gas-phase fragmentation of a peptic fragment prior to MS analysis is a promising technique to further increase the resolution. The biggest technical challenge for this method is elimination of intramolecular hydrogen/deuterium exchange (scrambling) in the gas phase. The scrambling obscures the location of deuterium...
February 13, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28152598/immuno-affinity-capture-followed-by-tmpp-n-terminus-tagging-to-study-catabolism-of-therapeutic-proteins
#3
Majlinda Kullolli, Dan A Rock, Ji Ma
Characterization of in vitro and in vivo catabolism of therapeutic proteins has increasingly become an integral part of discovery and development process for novel proteins. Unambiguous and efficient identification of catabolites can not only facilitate accurate understanding of pharmacokinetic profiles of drug candidates, but also enables follow up protein engineering to generate more catabolically stable molecules with improved properties (pharmacokinetics and pharmacodynamics). Immunoaffinity capture (IC) followed by top-down intact protein analysis using either matrix-assisted laser desorption/ionization or electrospray ionization mass spectrometry analysis have been the primary methods of choice for catabolite identification...
February 3, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28135243/hormonal-gain-control-of-a-medial-preoptic-area-social-reward-circuit
#4
Jenna A McHenry, James M Otis, Mark A Rossi, J Elliott Robinson, Oksana Kosyk, Noah W Miller, Zoe A McElligott, Evgeny A Budygin, David R Rubinow, Garret D Stuber
Neural networks that control reproduction must integrate social and hormonal signals, tune motivation, and coordinate social interactions. However, the neural circuit mechanisms for these processes remain unresolved. The medial preoptic area (mPOA), an essential node for social behaviors, comprises molecularly diverse neurons with widespread projections. Here we identify a steroid-responsive subset of neurotensin (Nts)-expressing mPOA neurons that interface with the ventral tegmental area (VTA) to form a socially engaged reward circuit...
January 30, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28130052/pharmacological-activation-of-the-neurotensin-receptor-1-abrogates-the-methamphetamine-induced-striatal-apoptosis-in-the-mouse-brain
#5
Qingkun Liu, Ariela Hazan, Eddie Grinman, Jesus A Angulo
Methamphetamine (METH) is a widely abused psychostimulant displaying potent addictive and neurotoxic properties. METH induces neurotoxicity of dopaminergic terminals and striatal neurons in the striatum. Despite much information on neurotransmitters, the role of neuropeptides is poorly understood. In this study, we investigated the role of the neuropeptide neurotensin on the METH-induced apoptosis of some striatal neurons in mice. We observed that a single injection of METH (30 mg/kg, ip) induced the loss of approximately 15% of striatal neurons...
January 24, 2017: Brain Research
https://www.readbyqxmd.com/read/28127518/the-lack-of-association-between-angiotensin-converting-enzyme-gene-insertion-deletion-polymorphism-and-nicotine-dependence-in-multiple-sclerosis
#6
Sergej Nadalin, Alena Buretić-Tomljanović, Polona Lavtar, Nada Starčević Čizmarević, Alenka Hodžić, Juraj Sepčić, Miljenko Kapović, Borut Peterlin, Smiljana Ristić
OBJECTIVE: Blood-borne angiotensin II is generated from angiotensinogen via cleavage by renin and angiotensin-converting enzyme (ACE), an enzymatic cascade known as the renin-angiotensin system (RAS). Several lines of evidence indicate that ACE, beyond its classical role of mediating blood pressure regulation, might contribute to the etiology of substance addictions by influencing dopaminergic signaling. A functional insertion/deletion (I/D) polymorphism of the ACE gene was associated with risk for being a smoker among individuals with depression and with smoking severity in studies comprising patients with depression and healthy controls...
January 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28117023/an-overview-of-bioactive-peptides-for-in-vivo-imaging-and-therapy-in-human-diseases
#7
Anna Lucia Tornesello, Maria Lina Tornesello, Franco M Buonaguro
Radiolabeled peptides, designed to bind with high affinity receptors selectively expressed on cell membranes of different human tissues, represent valuable tools for in vivo imaging of several human diseases. Solid-phase peptide synthesis as well as availability of bifunctional chelating agents and prosthetic groups allows the production and radiolabeling of several peptide-based molecules which are useful to target specific receptors on different cancer types. Among them, octreotide and other analogues of somatostatin, vasoactive intestinal peptide, CCK analogues, bombesin, α-MSH analogues, neurotensin, exendin, RGD substance P, conjugated to appropriate chelators, such as DTPA, NOTA, DOTA or TETA, and radiolabeled with specific radionuclides, have already been translated into the clinical practice with remarkable sensitivity and diagnostic accurateness...
January 20, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28115552/xenin-augments-duodenal-anion-secretion-via-activation-of-afferent-neural-pathways
#8
Izumi Kaji, Yasutada Akiba, Ikuo Kato, Koji Maruta, Atsukazu Kuwahara, Jonathan D Kaunitz
Xenin-25, a neurotensin (NT)-related anorexigenic gut hormone generated mostly in the duodenal mucosa, is believed to increase the rate of duodenal ion secretion, since xenin-induced diarrhea is not present after Roux-en-Y gastric bypass surgery. Since the local effects of xenin on duodenal ion secretion have remained uninvestigated, we thus examined the neural pathways underlying xenin-induced duodenal anion secretion. Intravenous infusion of xenin-8, a bioactive C-terminal fragment of xenin-25, dose-dependently increased the rate of duodenal HCO3- secretion in perfused duodenal loops of anesthetized rats...
January 23, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28108848/glucagon-like-peptide-1-is-co-localized-with-neurotensin-in-the-chicken-ileum
#9
Kei Nishimura, Kohzy Hiramatsu, Takafumi Watanabe, Kazumi Kita
Glucagon-like peptide (GLP)-1 and neurotensin (NT) are distributed throughout the chicken ileum. Here, we attempt to determine if GLP-1 and NT co-localize in the chicken ileum by using immunofluorescence, immunocytochemistry and in situ hybridization techniques. Three types of enteroendocrine cells, GLP-1(+)/NT(+), GLP-1(+)/NT(-) and GLP-1(-)/NT(+) cells, were detected in the mucosal epithelium by the double immunofluorescence method. The ratio of GLP-1(+)/NT(+) cells at the crypts in the distal ileum was significantly higher than that in the proximal ileum...
January 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28094875/neuroendocrinology-of-mast-cells-challenges-and-controversies
#10
REVIEW
Theoharis C Theoharides
Mast cells (MC) are hemopoietically-derived tissue immune cells that are ubiquitous in the body, including neuroendocrine organs such as the hypothalamus, pineal, pituitary, ovaries, pancreas and uterus where their action is not well understood. Mast cells have historically been associated with allergies because of their rich content of histamine and tryptase, but more recently with regulation of immunity and inflammation due their synthesis and release of numerous cytokines and chemokines. Mast cells are located perivascularly and express numerous receptors for diverse ligands such as allergens, pathogens, neurotransmitters, neuropeptides and hormones including acetylcholine, calcitonin gene-related peptide (CGRP), corticosteroids, corticotropin-releasing hormone (CRH), β-endorphin, epinephrine, 17β-estradiol, gonadotrophins, hemokinin-A (HKA), leptin, melatonin, neurotensin (NT), parathyroid hormone (PTH), substance P (SP) and vasoactive instestinal peptide (VIP)...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28089918/cardiovascular-and-respiratory-activity-of-pk20-opioid-and-neurotensin-hybrid-peptide-in-anesthetized-and-awake-rats
#11
Katarzyna Kaczyńska, Piotr Wojciechowski, Monika Jampolska, Andrzej W Lipkowski, Patrycja Kleczkowska
AIM: Chimeric compound - PK20 despite its therapeutic activity on nociceptive and inflammatory processes may affect respiration and blood pressure. Our objective was to evaluate influence of the hybrid composed of endomorphin-2 and neurotensin fragments on ventilation, heart rate and blood pressure in anesthetized and awake rats. METHODS: The effects of PK20 (1mg/kg) were studied either after its intravenous administration in anesthetized rats or intraperitoneal injection in awake state...
January 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28089664/neurotensin-nts1-and-nts2-receptor-agonists-produce-anxiolytic-like-effects-in-the-22-khz-ultrasonic-vocalization-model-in-rats
#12
Floyd F Steele, Shannon C Whitehouse, Jacob S Aday, Adam J Prus
Neurotensin is a neuropeptide neurotransmitter that interacts with multiple neurotransmitter systems, including those regulating amygdalar function, via NTS1 and NTS2 receptors. Both receptors are expressed in the amygdala and agonists for NTS1 or NTS2 receptors have exhibited anxiolytic effects in animal models. Systemic adminstration of NTS1 receptor agonist PD149163 was recently shown to reduce footshock conditioned 22-kHz ultrasonic vocalizations in rats, suggesting that PD149163 produced an anxiolytic effect...
January 12, 2017: Brain Research
https://www.readbyqxmd.com/read/28032980/ligand-discovery-for-a-peptide-binding-gpcr-by-structure-based-screening-of-fragment-and-lead-like-chemical-libraries
#13
Anirudh Ranganathan, Philipp Heine, Axel Rudling, Andreas Plückthun, Lutz Kummer, Jens Carlsson
Peptide-recognizing G protein-coupled receptors (GPCRs) are promising therapeutic targets, but often resist drug discovery efforts. Determination of crystal structures for peptide-binding GPCRs has provided opportunities to explore structure-based methods in lead development. Molecular docking screens of two chemical libraries, containing either fragment- or lead-like compounds, against a Neurotensin receptor 1 crystal structure allowed for a comparison between different drug development strategies for peptide-binding GPCRs...
December 29, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/28028605/neuropeptide-systems-and-new-treatments-for-nicotine-addiction
#14
REVIEW
Adriaan W Bruijnzeel
RATIONALE: The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. OBJECTIVES: The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking...
December 28, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27995402/does-the-ileal-brake-contribute-to-delayed-gastric-emptying-after-pancreatoduodenectomy
#15
REVIEW
Savio G Barreto, John A Windsor
Delayed gastric emptying (DGE) represents a significant cause for morbidity following pancreatoduodenectomy (PD). At a time when no specific and universally effective therapy exists to treat these patients, elucidating other potential (preventable or treatable) mechanisms for DGE is important. The aim of the manuscript was to test the hypothesis that ileal brake contributes to DGE in PD patients receiving jejunal tube feeding by systematically reviewing experimental and clinical literature. A series of clinically relevant questions were framed related to the potential role of the ileal brake in development of DGE post-PD and formed the basis of targeted literature searches...
December 19, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27932946/increased-brain-neurotensin-and-ntsr2-lead-to-weak-nociception-in-ntsr3-sortilin-knockout-mice
#16
Christelle Devader, Sébastien Moreno, Morgane Roulot, Emmanuel Deval, Thomas Dix, Carlos R Morales, Jean Mazella
The neuropeptide neurotensin (NT) elicits numerous pharmacological effects through three different receptors (NTSR1, NTSR2, and NTSR3 also called sortilin). Pharmacological approaches and generation of NTSR1 and NTSR2-deficient mice allowed to determine the NT-induced antipsychotic like behavior, the inhibitory of weak fear memory and the nociceptive signaling in a rat formalin tonic pain model to NTSR1. Conversely, the effects of NT on thermal and tonic nociceptions were mediated by NTSR2. However, the role of NTSR3/sortilin on the neurotensinergic system was not investigated...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27924846/structure-and-dynamics-of-a-constitutively-active-neurotensin-receptor
#17
Brian E Krumm, Sangbae Lee, Supriyo Bhattacharya, Istvan Botos, Courtney F White, Haijuan Du, Nagarajan Vaidehi, Reinhard Grisshammer
Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3 Å crystal structure of a constitutively active, agonist-bound neurotensin receptor (NTSR1) and molecular dynamics simulations of agonist-occupied and ligand-free receptor. Comparison with the structure of a NTSR1 variant that has little constitutive activity reveals uncoupling of the ligand-binding domain from conserved connector residues, that effect conformational changes during GPCR activation...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27914862/neurotensin-regulation-induces-overexpression-and-activation-of-egfr-in-hcc-and-restores-response-to-erlotinib-and-sorafenib
#18
Zherui Wu, Antoine Galmiche, Jin Liu, Nicolas Stadler, Dominique Wendum, Evelyne Segal-Bendirdjian, Valerie Paradis, Patricia Forgez
Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer due to the combination of late diagnosis and a lack of curative treatments. The identification of factors which promote tumor aggressiveness, and those that predict treatment responses, are a means to optimize the management of HCC patients. The complex of Neurotensin (NTS) and its high affinity receptor (NTSR1) has been shown to induce tumor growth and metastasis process in various cancers. In this paper, we propose that NTS and NTSR1 can assist in the management of HCC...
December 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27902570/preprotachykinin-a-is-expressed-by-a-distinct-population-of-excitatory-neurons-in-the-mouse-superficial-spinal-dorsal-horn-including-cells-that-respond-to-noxious-and-pruritic-stimuli
#19
Maria Gutierrez-Mecinas, Andrew M Bell, Alina Marin, Rebecca Taylor, Kieran A Boyle, Takahiro Furuta, Masahiko Watanabe, Erika Polgár, Andrew J Todd
The superficial dorsal horn, which is the main target for nociceptive and pruritoceptive primary afferents, contains a high density of excitatory interneurons. Our understanding of their roles in somatosensory processing has been restricted by the difficulty of distinguishing functional populations among these cells. We recently defined 3 nonoverlapping populations among the excitatory neurons, based on the expression of neurotensin, neurokinin B, and gastrin-releasing peptide. Here we identify and characterise another population: neurons that express the tachykinin peptide substance P...
March 2017: Pain
https://www.readbyqxmd.com/read/27891817/preliminary-study-of-personality-traits-in-chinese-lung-cancer-patients-modification-by-neurotensin-receptor-1-polymorphisms
#20
Hui Ma, Zhengtu Cong, Hongyu Zhang, Jiangang Tao, Chao Yang, Zhijie Song
This study recruited 148 lung cancer patients and 157 healthy Chinese individuals to evaluate the personality traits of Chinese lung cancer patients using the Tridimensional Personality Questionnaire and to investigate the associations between these traits and the rs6090453C/G and rs6011914C/G polymorphisms of the neurotensin receptor 1 gene. The results demonstrated significant differences in the Tridimensional Personality Questionnaire total and subscale scores between the 2 groups. Significant differences were found in the reward dependence 2 (RD2) score between the rs6090453C/G genotypes and in the total harm avoidance (HA), HA1, HA2, HA4, and RD2 scores between the rs6011914C/G genotypes...
November 28, 2016: Asia-Pacific Psychiatry: Official Journal of the Pacific Rim College of Psychiatrists
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