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tryptophan hydroxylase

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https://www.readbyqxmd.com/read/29194046/updates-on-the-biology-of-serotonin-and-tryptophan-hydroxylase
#1
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...
November 30, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/29174640/dorsal-raph%C3%A3-nucleus-glucocorticoid-receptors-inhibit-tph2-gene-expression-in-male-c57bl-6j-mice
#2
Melanie Y Vincent, Nina C Donner, David G Smith, Christopher A Lowry, Lauren Jacobson
The serotonergic dorsal raphé nucleus (DRN) expresses glucocorticoid receptors (GR), and systemic glucocorticoids have been shown to regulate expression and activity of tryptophan hydroxylase isoform 2, the rate-limiting enzyme for serotonin synthesis in brain. We have used intra-DRN injection of pseudotyped adeno-associated virus AAV2/9 transducing either green fluorescent protein (GFP control) or Cre recombinase (DRN GR deletion) in floxed GR mice to determine if DRN GR directly regulate DRN mRNA levels of tryptophan hydroxylase 2 (tph2)...
November 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29172658/-tetrahydrobiopterin-bh4-deficiency-diagnosis-and-treatment
#3
János Bókay
Since the initial breaking discovery of Følling that the severe neurological consequences of phenylketonuria could be prevented by use of low phenylalanine (Phe) diet, it has been shortly recognised that defective phenylalanine metabolism may also arise from the deficiency of tetrahydrobiopterin (BH4) cofactor, required for phenylalanine-hydroxylase activity. Furthermore, as BH4 is in Phe metabolism, it is also a cofactor for the activities of tyrosine hydroxylase and tryptophane hydroxylase, enzymes required for the synthesis of catecholamines and serotonin neurotransmitters...
December 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/29133842/serotonin-regulates-prostate-growth-through-androgen-receptor-modulation
#4
Emanuel Carvalho-Dias, Alice Miranda, Olga Martinho, Paulo Mota, Ângela Costa, Cristina Nogueira-Silva, Rute S Moura, Natalia Alenina, Michael Bader, Riccardo Autorino, Estêvão Lima, Jorge Correia-Pinto
Aging and testosterone almost inexorably cause benign prostatic hyperplasia (BPH) in Human males. However, etiology of BPH is largely unknown. Serotonin (5-HT) is produced by neuroendocrine prostatic cells and presents in high concentration in normal prostatic transition zone, but its function in prostate physiology is unknown. Previous evidence demonstrated that neuroendocrine cells and 5-HT are decreased in BPH compared to normal prostate. Here, we show that 5-HT is a strong negative regulator of prostate growth...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29126768/increased-functional-coupling-of-5-ht1a-autoreceptors-to-girk-channels-in-tph2-mice
#5
Boris Mlinar, Alberto Montalbano, Jonas Waider, Klaus-Peter Lesch, Renato Corradetti
Firing activity of serotonergic neurons is under regulatory control by somatodendritic 5-HT1A autoreceptors (5-HT1AARs). Enhanced 5-HT1AAR functioning may cause decreased serotonergic signaling in brain and has thereby been implicated in the etiology of mood and anxiety disorders. Tryptophan hydroxylase-2 knockout (Tph2(-/-)) mice exhibit sensitization of 5-HT1A agonist-induced inhibition of serotonergic neuron firing and thus represents a unique animal model of enhanced 5-HT1AAR functioning. To elucidate the mechanisms underlying 5-HT1AAR supersensitivity in Tph2(-/-) mice, we characterized the activation of G protein-coupled inwardly-rectifying potassium (GIRK) conductance by the 5-HT1A receptor agonist 5-carboxamidotryptamine using whole-cell recordings from serotonergic neurons in dorsal raphe nucleus...
November 7, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29125838/nitrergic-neurons-of-the-dorsal-raphe-nucleus-encode-information-about-stress-duration
#6
India S Nichols, Mary I Jones, Chuma Okere, Godwin Ananaba, Brittany Bush, Cloe Gray, Allison Brager, J Christopher Ehlen, Ketema Paul
Nitrergic neurons of the dorsal raphe nucleus (DRN) may play a role in physiological stress responses. The caudal lateral wings (CLW) are unique compared to other rostral-caudal DRN sub-regions because they contain distinct nitric oxide (NO) synthase (NOS) populations that are independent of tryptophan hydroxylase (TPH). NOS neurons in the CLW are also highly activated during acute restraint stress. However, the effects of acute stress duration on NOS activation in the CLW are unclear. Here NADPH-d, an index of NOS activity, is used to show that sub-regions of the DRN have differential NOS activation in response to 6 hours of restraint stress in rats...
2017: PloS One
https://www.readbyqxmd.com/read/29123193/characterization-of-mammary-specific-disruptions-for-tph1-and-lrp5-during-murine-lactation
#7
Samantha R Weaver, Nicholas J Jury, Karen A Gregerson, Nelson D Horseman, Laura L Hernandez
Serotonin is a homeostatic regulator of the mammary gland during lactation. The contribution of mammary-derived serotonin to circulating serum serotonin concentrations was previously unknown. We have developed mice with mammary-specific disruptions of tryptophan hydroxylase 1 (Tph1) or low-density lipoprotein receptor-related protein 5 (Lrp5) that are induced during late pregnancy and lactation via use of the whey acidic protein (WAP)-Cre cre-lox system. Our objective was to characterize dams with a lactation- and mammary-specific disruption of Lrp5 (WAP-Cre × Lrp5 (FL/FL)) or Tph1 (WAP-Cre × Tph1 (FL/FL))...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29074312/understanding-the-patient-experience-with-carcinoid-syndrome-exit-interviews-from-a-randomized-placebo-controlled-study-of-telotristat-ethyl
#8
Lowell Anthony, Claire Ervin, Pablo Lapuerta, Matthew H Kulke, Pamela Kunz, Emily Bergsland, Dieter Hörsch, David C Metz, Janice Pasieka, Nick Pavlakis, Marianne Pavel, Martyn Caplin, Kjell Öberg, John Ramage, Emily Evans, Qi Melissa Yang, Shanna Jackson, Karie Arnold, Linda Law, Dana B DiBenedetti
PURPOSE: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in TELESTAR, a Phase III study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview substudy was conducted to provide insight into the patient experience in TELESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful...
October 23, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/29067122/analgesic-activity-of-cynaropicrinon-on-post-inflammatory-irritable-bowel-syndrome-visceral-hypersensitivity-in-a-rat-model
#9
Hailong Shi, Xianwei Zhu, Yaya Cui, Yifei Qin, Lin Yang, Xu Deng
Visceral hypersensitivity is one of the most common symptoms in patients with post-inflammatory-irritable bowel syndrome (PI-IBS). Enterochromaffin (EC) cells and 5-hydroxytryptamine (5-HT) are important in the development of visceral hyperalgesia, and EC cells are influenced by helper T-cell subtype 1 or 2 cytokine predominant environments. In the present study, the analgesic effect of cynaropicrin and its underlying mechanism on the treatment of trinitrobenzene sulfonic (TNBS)-induced PI-IBS visceral hyperalgesia rats was investigated...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29051994/telotristat-ethyl-proof-of-principle-and-the-first-oral-agent-in-the-management-of-well-differentiated-metastatic-neuroendocrine-tumor-and-carcinoid-syndrome-diarrhea
#10
REVIEW
Muhammad Masab, Muhammad Wasif Saif
INTRODUCTION: Metastatic neuroendocrine tumors (NETs) are associated with carcinoid syndrome that is typically characterized by diarrhea, cutaneous flushing and bronchospasm. Treatment with somatostatin analogues (SSA) improves the symptom burden but a significant proportion of patients stop responding to SSA therapy eventually. Novel agents with the potential to effectively control the symptoms are urgently needed. METHODS: This article reviews an in-depth analysis of the phase I-III clinical trials determining the clinical rationale for the use of tryptophan hydroxylase inhibitor, telotristat ethyl in patients with well-differentiated metastatic NETs and uncontrolled carcinoid syndrome...
October 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29046318/central-serotonin-and-the-control-of-arterial-blood-pressure-and-heart-rate-in-infant-rats-influence-of-sleep-state-and-sex
#11
Jennifer L Magnusson, Kevin James Cummings
Sudden Infant Death Syndrome (SIDS) is associated with serotonin (5-HT) neuron abnormalities. There is evidence of autonomic dysfunction during sleep in infants eventually succumbing to SIDS, as well as cardiovascular collapse prior to death. Neonatal rodents deficient in central 5-HT display hypotension and bradycardia. We hypothesized that central 5-HT reduces cardiac vagal tone and increases sympathetic vascular tone and, given the firing pattern of 5-HT neurons, that these effects are greater in quiet sleep (QS) than in active sleep (AS)...
October 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29035920/the-antidepressant-like-effects-of-sinomenine-in-mice-a-behavioral-and-neurobiological-characterization
#12
Xiuqin Li, Chao Liu, Bo Jiang, Kai Chen, Wenjuan Li, Hongze Wang
Sinomenine is a bioactive alkaloid extracted from Sinomenium acutum. Here, we investigated the antidepressant effects of sinomenine in mice. The antidepressant actions of sinomenine were first examined in the forced-swim test and the tail-suspension test, and then assessed in the chronic social defeat stress (CSDS) model of depression. Changes in the brain-derived neurotrophic factor (BDNF) signaling pathway after CSDS and sinomenine treatment were also investigated. A tryptophan hydroxylase inhibitor and a BDNF signaling inhibitor were also used to determine the pharmacological mechanisms of sinomenine...
October 13, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29035515/isoform-specific-substrate-inhibition-mechanism-of-human-tryptophan-hydroxylase
#13
Kasper D Tidemand, Günther H Peters, Pernille Harris, Eva Stensgaard, Hans E M Christensen
Tryptophan hydroxylase (TPH) catalyzes the initial and rate-limiting step in the biosynthesis of serotonin, which is associated with a variety of disorders such as depression and irritable bowel syndrome. TPH exists in two isoforms: TPH1 and TPH2. TPH1 catalyzes the initial step in the synthesis of serotonin in the peripheral tissues, while TPH2 catalyzes this step in the brain. In this study, the steady-state kinetic mechanism for the catalytic domain of human TPH1 has been determined. Varying substrate tryptophan (Trp) and tetrahydrobiopterin (BH4) results in a hybrid Ping Pong-ordered mechanism in which the reaction can either occur through a Ping Pong or a sequential mechanism depending on the concentration of tryptophan...
October 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/29031405/life-span-resolved-nanotoxicology-enables-identification-of-age-associated-neuromuscular-vulnerabilities-in-the-nematode-caenorhabditis-elegans
#14
Annette Piechulek, Anna von Mikecz
At present, the majority of investigations concerning nanotoxicology in the nematode C. elegans address short-term effects. While this approach allows for the identification of uptake pathways, exposition and acute toxicity, nanoparticle-organism interactions that manifest later in the adult life of C. elegans are missed. Here we show that a microhabitat composed of liquid S-medium and live bacteria in microtiter wells prolongs C. elegans longevity and is optimally suited to monitor chronic eNP-effects over the entire life span (about 34 days) of the nematode...
October 11, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28991991/effects-of-ghrelin-on-nocturnal-melatonin-secretion-in-sheep-an-in-vitro-and-in-vivo-approach
#15
K Kirsz, M Szczesna, E Molik, D A Zieba
Recent studies confirmed that pineal melatonin (MEL) secretion is regulated by ghrelin (GHRL) in seasonally reproductive sheep. The first in vivo experiment investigated whether the effect of GHRL on nocturnal secretion of MEL in sheep is mediated by type 2 serotonin receptors. Sheep ( = 16) were intravenously injected with GHRL (2.5 μg/kg of BW) and meta-Chlorophenylpiperazine (mCPP; a mixed agonist of 5-HT2B/5-HT2C receptors; 1 mg/kg BW), either combined or individually, during the short-day (SDS) and long-day (LDS) seasons...
September 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28972592/genetically-driven-brain-serotonin-deficiency-facilitates-panic-like-escape-behavior-in-mice
#16
J Waider, S Popp, M D Lange, R Kern, J F Kolter, J Kobler, N C Donner, K R Lowe, J H Malzbender, C J Brazell, M R Arnold, B Aboagye, A Schmitt-Böhrer, C A Lowry, H C Pape, K P Lesch
Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings...
October 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28968985/stress-inhibits-tryptophan-hydroxylase-expression-in-a-rat-model-of-depression
#17
Yi Chen, Haixia Xu, Mingyue Zhu, Kun Liu, Bo Lin, Ruxian Luo, Chuanbai Chen, Mengsen Li
Serotonin (5-hydroxytryptamine, 5-HT) dysfunction is associated with the pathophysiology of depression. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, is believed to have essential role in many mental disorders, including depression. In the present study, we generated a rat model of depression by exposing the animals to stress, and the rats were then treated with paroxetine. The results indicated that the concentration of 5-HT in the brain and liver tissues were significantly lower in the rat model of depression than in healthy or treated rats...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28948742/-effects-of-baldrinal-of-valeriana-jatamansi-on-expression-of-crf-tph1-mrna-and-5-ht-in-rats-with-irritable-bowel-syndrome
#18
Si-Yu Tao, Cong-Rui Xiao, Jing Wang, Shu-Jing Zhang, Yu-Shan Gao, Fang-Yuan Mu, Yi-Cheng Wang, Xing-Li Yan
This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group...
January 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28939428/cd36-is-a-candidate-lipid-sensor-involved-in-the-sensory-detection-of-fatty-acid-in-zebrafish
#19
Haiyang Liu, Yanping Xu, Ying Wang, Shenjie Zhong, Min Wang, Pengyan Lin, Hongyan Li, Zhenhui Liu
Recently more and more evidences raise the possibility for the taste system in the role of the perception of lipids in mammals, and the fatty acid receptor CD36 has been proved to be as an important candidate receptor of fat taste. Fish has different taste modality with mammals. No information was known about the function of cd36 in fish taste till now. Here, using in situ hybridization and immunofluorescence technologies, we showed that fish cd36/Cd36 localized in taste buds. Real-time PCR technology demonstrated that, in zebrafish cd36 (zcd36)-transfected cells, linoleic acid (LA) increased the expression level of tryptophan hydroxylase-1 (TPH-1), which encodes the enzyme involved in the biosynthesis of monoamine neurotransmitter of 5-HT...
December 1, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28933662/deficiency-of-serotonin-in-raphe-neurons-and-altered-behavioral-responses-in-tryptophan-hydroxylase-2-knockout-medaka-oryzias-latipes
#20
Satoshi Ansai, Hiroshi Hosokawa, Shingo Maegawa, Kiyoshi Naruse, Youhei Washio, Kenji Sato, Masato Kinoshita
Serotonin (5-hydroxytryptamine [5-HT]) is a bioactive monoamine that acts as a neurotransmitter in the central and peripheral nervous system of animals. Teleost fish species have serotonergic neurons in the raphe nuclei of the brainstem; however, the role of 5-HT in the raphe neurons in teleost fish remains largely unknown. Here, we established a medaka (Oryzias latipes) strain with targeted disruption of tryptophan hydroxylase 2 (tph2) gene that is involved in the 5-HT synthesis in the raphe nuclei. Immunohistochemistry and mass spectrometry analysis revealed that the homozygous mutants (tph2(Δ13/Δ13)) lacked the ability to synthesize 5-HT in the raphe neurons...
September 21, 2017: Zebrafish
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