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tryptophan hydroxylase

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https://www.readbyqxmd.com/read/29447434/alterations-in-melatonin-and-serotonin-signalling-in-the-colonic-mucosa-of-mice-with-dextran-sodium-sulfate-induced-colitis
#1
Sarah J MacEachern, Catherine M Keenan, Evangelia Papakonstantinou, Keith A Sharkey, Bhavik Anil Patel
BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal serotonin (5-HT) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co-released with 5-HT from the mucosa and has a wide variety of actions in the GI tract. Here we examined how melatonin signalling is affected by colitis and determined how this relates to 5-HT signalling. EXPERIMENTAL APPROACH: Using electroanalytical approaches, we investigated how 5-HT release, reuptake and availability as well as melatonin availability are altered in dextran sodium sulfate (DSS)-induced colitis in mice...
February 15, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29436197/the-role-of-serotonin-in-ventricular-repolarization-in-pregnant-mice
#2
Shanyu Cui, Hyewon Park, Hyelim Park, Dasom Mun, Seung Hyun Lee, Hyoeun Kim, Nuri Yun, Hail Kim, Michael Kim, Hui Nam Pak, Moon Hyoung Lee, Boyoung Joung
PURPOSE: The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. MATERIALS AND METHODS: We measured current amplitudes and the expression levels of voltage-gated K⁺ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a(-/-)-NP)...
March 2018: Yonsei Medical Journal
https://www.readbyqxmd.com/read/29432787/possible-involvement-of-monoamine-neurons-in-the-emotional-abnormality-in-kir6-2-deficient-mice
#3
Atsumi Saito, Kazuya Miyagawa, Hiroko Miyagishi, Kazuhiro Kurokawa, Akira Umeda, Yasumasa Okada, Minoru Tsuji, Hiroshi Takeda
ATP-sensitive potassium (KATP) channels consist of two structurally different subunits: a pore-forming subunit of the Kir6.0-family (Kir6.1 or Kir6.2) and a regulatory sulfonylurea receptor subunit (SUR1, SUR2A or SUR2B). Although Kir6.2 is widely distributed in the brain, the mechanisms that underlie the impact of Kir6.2 on emotional behavior are not yet fully understood. To clarify the role of Kir6.2 in emotional behavior, in the present study, we investigated the behavioral characteristics of Kir6.2-knockout (Kir6...
February 9, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29421749/increased-coiling-frequency-linked-to-apoptosis-in-the-brain-and-altered-thyroid-signaling-in-zebrafish-embryos-danio-rerio-exposed-to-the-pbde-metabolite-6-oh-bde-47
#4
Feng Wang, Mingliang Fang, David E Hinton, Melissa Chernick, Shenglan Jia, Yingdan Zhang, Lingtian Xie, Wenjing Dong, Wu Dong
Polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants that are ubiquitously detected in the environment and associated with adverse health outcomes. 6-OH-BDE-47 is a metabolite of the flame retardant, 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), and there is increasing concern regarding its developmental neurotoxicity and endocrine disrupting properties. In this study, we report that early life exposure in zebrafish (Danio rerio) embryos to 6-OH-BDE-47 (50 and 100 nM) resulted in higher coiling frequency and significantly increased apoptotic cells in the brain...
February 3, 2018: Chemosphere
https://www.readbyqxmd.com/read/29410249/biphasic-effect-of-sumatriptan-on-ptz-induced-seizures-in-mice-modulation-by-5-ht1b-d-receptors-and-nos-no-pathway
#5
Maziar Gooshe, Keyvan Ghasemi, Mohammad Mojtaba Rohani, Abbas Tafakhori, Shayan Amiri, Vajiheh Aghamollaii, Mona Ahmadi, Ahmad Reza Dehpour
Sumatriptan has been among the top choices in the management of migraine headaches. The association between migraine and epilepsy highlights the possible effect of sumatriptan on seizures. In this regard, we investigated sumatriptan effects on PTZ-induced seizures thresholds and delineated the modulatory role of 5-HT1B/D receptors and NOS/NO pathway. Our data revealed the anti-convulsant effects of lower doses of sumatriptan, and pro-convulsant effects of higher doses of sumatriptan. GR 127935, a selective 5-HT1B/D antagonist, could abolish the sumatriptan anti-convulsant effects, but it was ineffective against the sumatriptan pro-convulsant effects...
February 2, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29382152/evaluation-of-melatonin-secretion-and-metabolism-exponents-in-patients-with-ulcerative-and-lymphocytic-colitis
#6
Cezary Chojnacki, Janusz Błasiak, Jakub Fichna, Jan Chojnacki, Tomasz Popławski
Inflammatory bowel diseases, particularly ulcerative colitis (UC) and lymphocytic colitis (LC), affect many people. The role of melatonin in the pathogenesis of UC is precisely determined, whereas in LC it remains unknown. The aim of this study was to compare the expression of the melatonin-synthesizing enzymes tryptophan hydroxylase (TPH1), arylalkylamine-N-acetyltransferase (AANAT), and N-acetylserotonin methyltransferase (ASMT) in the colonic mucosa and urinary excretion of 6-sulfatoxymelatonin in patients with ulcerative and lymphocytic colitis...
January 29, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29381782/pathway-of-maternal-serotonin-to-the-human-embryo-and-fetus
#7
Harvey J Kliman, Sarah B Quaratella, Alessandra C Setaro, Erin C Siegman, Zarrin T Subha, Reshef Tal, Kristin M Milano, Theodore L Steck
Serotonin (5-hydroxytryptamine; 5-HT) is essential to intrauterine development, but its source is debated. We used immunocytochemistry to gauge 5-HT; its biosynthetic enzyme (tryptophan hydroxylase 1, TPH1); an importer (serotonin transporter, 5-HTT/SERT/SLC6A); other transporters (P-glycoprotein 1 [P-gp/ABCB1], OCT3/SLC22A3 and gap junction connexin-43); and the 5-HT degradative enzyme (monoamine oxidase A, MAOA) in sections of placentas. In humans, 5-HT was faintly stained only in first trimester trophoblasts, while TPH1 was not seen at any stage...
January 26, 2018: Endocrinology
https://www.readbyqxmd.com/read/29367674/tryptophan-hydroxylase-trh-loss-of-function-mutations-induce-growth-and-behavioral-defects-in-daphnia-magna
#8
Claudia Rivetti, Bruno Campos, Benjamín Piña, Demetrio Raldúa, Yasuhiko Kato, Hajime Watanabe, Carlos Barata
Tryptophan hydroxylase (TRH) is the rate limiting enzyme in the serotonin synthesis. CRISPR-Cas9 technology was used to generate seven indel TRH mutants in Daphnia magna. Mono-allelic indel TRH-/+ clones showed normal levels of serotonin, measured by both immunohistochemistry and mass spectrometry (LC-MS/MS), whereas bi-allelic indel TRH-/- clones showed no detectable levels of serotonin. Life history and behavioral responses of TRH-/- clones showed the anti-phenotype of those exposed to selective serotonin reuptake inhibitors (SSRI)...
January 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29362726/effects-of-estrogen-therapy-on-the-serotonergic-system-in-an-animal-model-of-perimenopause-induced-by-4-vinylcyclohexen-diepoxide-vcd
#9
Nayara Pestana-Oliveira, Bruna Kalil, Cristiane Mota Leite, Ruither Oliveira Gomes Carolino, Lucas Kniess Debarba, Lucila Leico Kagohara Elias, José Antunes-Rodrigues, Janete A Anselmo-Franci
Chronic exposure to 4-vinylcycloxene diepoxide (VCD) in rodents accelerates the natural process of ovarian follicular atresia modelling perimenopause in women. We investigated why estrogen therapy is beneficial for symptomatic women despite normal or high estrogen levels during perimenopause. Female rats (28 d) were injected daily with VCD or oil for 15 d; 55-65 d after the first injection, pellets of 17β-estradiol or oil were inserted subcutaneously. Around 20 d after, the rats were euthanized (control rats on diestrus and estradiol-treated 21 d after pellets implants)...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29350062/telotristat-ethyl-a-novel-agent-for-the-therapy-of-carcinoid-syndrome-diarrhea
#10
Joseph S Dillon, Chandrikha Chandrasekharan
Carcinoid syndrome (CS), characterized by diarrhea and flushing, is present in 20% of patients with neuroendocrine tumors at diagnosis and becomes more frequent with progression. The diarrhea of CS is caused mainly by tumoral secretion of serotonin. It may not be fully controlled by somatostatin analogs, the currently indicated drugs for symptomatic relief. Telotristat ethyl is a novel inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in serotonin biosynthesis. Administration of the drug decreases diarrhea in patients with CS...
January 19, 2018: Future Oncology
https://www.readbyqxmd.com/read/29345193/serotonin-2a-receptor-inhibition-protects-against-the-development-of-pulmonary-hypertension-and-pulmonary-vascular-remodeling-in-neonatal-mice
#11
Cassidy Delaney, Laurie Sherlock, Susan Fisher, Joanne K Maltzahn, Clyde J Wright, Eva Nozik-Grayck
Pulmonary hypertension (PH) complicating bronchopulmonary dysplasia (BPD) worsens clinical outcomes in former preterm infants. Increased serotonin (5-hydroxytryptamine, 5-HT) signaling plays a prominent role in PH pathogenesis and progression in adults. We hypothesized that increased 5-HT signaling contributes to the pathogenesis of neonatal PH complicating BPD and neonatal lung injury. Thus, we interrogated 5-HT signaling in neonatal mice exposed to bleomycin, previously demonstrated to induce PH and alveolar simplification...
January 18, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29331172/blood-phenylalanine-reduction-corrects-cns-dopamine-and-serotonin-deficiencies-and-partially-improves-behavioral-performance-in-adult-phenylketonuric-mice
#12
Shelley R Winn, Tanja Scherer, Beat Thöny, Ming Ying, Aurora Martinez, Sydney Weber, Jacob Raber, Cary O Harding
Central nervous system (CNS) deficiencies of the monoamine neurotransmitters dopamine and serotonin have been implicated in the pathophysiology of neuropsychiatric dysfunction in human phenylketonuria (PKU). In this study, we confirmed the occurrence of brain dopamine and serotonin deficiencies in association with severe behavioral alterations and cognitive impairments in hyperphenylalaninemic C57BL/6-Pahenu2/enu2 mice, a model of human PKU. Phenylalanine-reducing treatments, including either dietary phenylalanine restriction or liver-directed gene therapy, initiated during adulthood were associated with increased brain monoamine content along with improvements in nesting behavior but without a change in the severe cognitive deficits exhibited by these mice...
January 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29330194/telotristat-ethyl-in-carcinoid-syndrome-safety-and-efficacy-in-the-telecast-phase-3-trial
#13
Marianne E Pavel, David J Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R P Warner, Matthew H Kulke, Lowell Anthony, Pamela Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio García-Carbonero
Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the Phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a Phase 3 companion study, assessed safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea, or elevated urinary 5-hydroxyindoleacetic acid [u5-HIAA]) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE)...
January 12, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29326893/treadmill-exercise-ameliorates-social-isolation-induced-depression-through-neuronal-generation-in-rat-pups
#14
Jung-Wan Cho, Sun-Young Jung, Sang-Won Lee, Sam-Jun Lee, Tae-Beom Seo, Young-Pyo Kim, Dae-Young Kim
Social isolation is known to induce emotional and behavioral changes in animals and humans. The effect of treadmill exercise on depression was investigated using social isolated rat pups. The rat pups in the social isolation groups were housed individually. The rat pups in the exercise groups were forced to run on treadmill for 30 min once a day from postnatal day 21 to postnatal day 34. In order to evaluate depression state of rat pups, forced swimming test was performed. Newly generated cells in the hippocampal dentate gyrus were determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry...
December 2017: Journal of Exercise Rehabilitation
https://www.readbyqxmd.com/read/29314569/association-between-single-nucleotide-polymorphisms-of-tph1-and-tph2-genes-and-depressive-disorders
#15
Paulina Wigner, Piotr Czarny, Ewelina Synowiec, Michał Bijak, Katarzyna Białek, Monika Talarowska, Piotr Galecki, Janusz Szemraj, Tomasz Sliwinski
Tryptophan catabolites pathway disorders are observed in patients with depression. Moreover, single nucleotide polymorphisms of tryptophan hydroxylase genes may modulate the risk of depression occurrence. The objective of our study was to confirm the association between the presence of polymorphic variants of TPH1 and TPH2 genes, and the development of depressive disorders. Six polymorphisms were selected: c.804-7C>A (rs10488682), c.-1668T>A (rs623580), c.803+221C>A (rs1800532), c.-173A>T (rs1799913)-TPH1, c...
January 5, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29310005/association-of-serotonergic-pathway-genes-with-smoking-cessation-in-a-chinese-rural-male-population
#16
Qiang Wang, Suyun Li, Huijie Li, Chongqi Jia
INTRODUCTION: Previous studies have found serotonergic pathway genes have inhibitory effects on dopamine system which may influence smoking addiction. This study examined the associations of serotonergic pathway genes (serotonergic receptor genes, solute carrier family 6 member4 and tryptophan hydroxylase gene) with smoking cessation. MATERIALS AND METHODS: Male current and former smokers (n=819) were recruited from 17 villages of three counties in Shandong province, China...
January 2, 2018: Addictive Behaviors
https://www.readbyqxmd.com/read/29297119/expression-of-components-of-the-serotonergic-system-in-the-developing-rat-thymus
#17
N V Lifantseva, Ts O Koneeva, E E Voronezhskaya, V I Melnikova
The developing thymus of rat fetuses contains all components of the serotonergic system: receptors, enzymes of synthesis, and membrane transporters. The expression of receptors suggests the possibility of a direct influence of serotonin on thymic development. The presence of tryptophan hydroxylase (the key rate-limiting enzyme of serotonin synthesis) and aromatic l-amino acid decarboxylase indicates the ability of fetal thymic cells to synthesize serotonin. It was shown that the cells of a developing thymus can actively uptake extracellular monoamines...
November 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29251109/human-olfactory-ensheathing-cell-transplantation-improves-motor-function-in-a-mouse-model-of-type-3-spinocerebellar-ataxia
#18
Jeanne Hsieh, Jen-Wei Liu, Horng-Jyh Harn, Kuo-Wei Hsueh, Karthyayani Rajamani, Yu-Chen Deng, Chih-Min Chia, Woei-Cheang Shyu, Shinn-Zong Lin, Tzyy-Wen Chiou
Spinocerebellar ataxia (SCA) is a progressive neurodegenerative disease that affects the cerebellum and spinal cord. Among the 40 types of SCA, SCA type 3 (SCA3), also referred to as Machado-Joseph disease, is the most common. In the present study, we investigated the therapeutic effects of intracranial transplantation of human olfactory ensheathing cells (hOECs) in the ATXN3-84Q mouse model of SCA3. Motor function begins to decline in ATXN3-84Q transgenic mice at approximately 13 weeks of age. ATXN3-84Q mice that received intracranial hOEC transplantation into the dorsal raphe nucleus of the brain exhibited significant improvements in motor function, as measured by the rotarod performance test and footprint pattern analysis...
October 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29223399/ectopic-serotonin-production-in-%C3%AE-cell-specific-transgenic-mice
#19
Hyeongseok Kim, Hyunki Kim, Kyuho Kim, Michael S German, Hail Kim
Genetically modified mice have been widely used in the field of β-cell research. However, analysis of results gathered using genetically modified organisms should be interpreted carefully as the results may be confounded by several factors. Here, we showed the ectopic serotonin (5-HT) production in β-cells of RIP-CreMgn, MIP-GFP, and MIP-Cre/ERT. These mice contained a human growth hormone (hGH) cassette to enhance transgene expression and hGH expression and Stat5 phosphorylation were detected in pancreatic islets of these mice...
December 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29194046/updates-on-the-biology-of-serotonin-and-tryptophan-hydroxylase
#20
Tara Swami, H Christian Weber
PURPOSE OF REVIEW: To summarize the most recent findings relevant to the biology of serotonin (5-hydroxytryptamine; 5-HT) and the enzyme tryptophan hydroxylase (TPH) in human gastrointestinal disease. RECENT FINDINGS: Serotonin is synthesized in the central nervous system (CNS) and the gastrointestinal tract where it is secreted from enteroendocrine cells. Its biosynthesis is regulated by two isoforms of the enzyme TPH of which TPH1 is localized predominantly in gastrointestinal enteroendocrine cells...
February 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
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