Expression of serotonin receptor genes in cranial ganglia

UNSTRUCTURED In the effort to improve treatment effectiveness in glioblastoma, this short note reviewed collected data on the pathophysiology of glioblastoma with particular reference to intersections with the pharmacology of perphenazine. That study identified five areas of potentially beneficial intersection. Data showed seemingly 5 independent perphenazine attributes of benefit to glioblastoma treatment - i) blocking dopamine receptor 2, ii) reducing centrifugal migration of subventricular zone cells by blocking dopamine receptor 3, iii) blocking serotonin receptor 7, iv) activation of protein phosphatase 2, and v) nausea reduction. Perphenazine is fully compatible with current chemoirradiation protocols and with the commonly used ancillary medicines used in clinical practice during the course of glioblastoma. All these attributes argue for a trial of perphenazine’s addition to current standard treatment with temozolomide and irradiation. The subventricular zone seeds the brain with mutated cells that become recurrent glioblastoma after centrifugal migration. The current paper shows how perphenazine might reduce that contribution. Perphenazine is an old, generic, cheap, phenothiazine antipsychotic drug that has been in continuous clinical use worldwide since the 1950’s. Clinical experience and research data over these decades have shown perphenazine to be well-tolerated in psychiatric populations, in normals, and in non-psychiatric, medically ill populations for whom perphenazine is used to reduce nausea. For now (Summer, 2020) the nature of glioblastoma requires a polypharmacy approach until/unless a core feature and means to address it can be identified in the future. Conclusions: Perphenazine possesses a remarkable constellation of attributes that recommend its use in GB treatment.

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Vitamin B6 deficiency disrupts serotonin signaling in pancreatic islets and induces gestational diabetes in mice

Communications Biology ◽

10.1038/s42003-021-01900-0 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Ashley M. Fields ◽

Kevin Welle ◽

Elaine S. Ho ◽

Clementina Mesaros ◽

Martha Susiarjo

Keyword(s):

Cell Proliferation ◽

Insulin Secretion ◽

Pancreatic Islets ◽

Glucose Intolerance ◽

Vitamin B6 ◽

Serotonin Receptor ◽

Dependent Manner ◽

Β Cell ◽

Vitamin B6 Deficiency ◽

Maternal Glucose

AbstractIn pancreatic islets, catabolism of tryptophan into serotonin and serotonin receptor 2B (HTR2B) activation is crucial for β-cell proliferation and maternal glucose regulation during pregnancy. Factors that reduce serotonin synthesis and perturb HTR2B signaling are associated with decreased β-cell number, impaired insulin secretion, and gestational glucose intolerance in mice. Albeit the tryptophan-serotonin pathway is dependent on vitamin B6 bioavailability, how vitamin B6 deficiency impacts β-cell proliferation during pregnancy has not been investigated. In this study, we created a vitamin B6 deficient mouse model and investigated how gestational deficiency influences maternal glucose tolerance. Our studies show that gestational vitamin B6 deficiency decreases serotonin levels in maternal pancreatic islets and reduces β-cell proliferation in an HTR2B-dependent manner. These changes were associated with glucose intolerance and insulin resistance, however insulin secretion remained intact. Our findings suggest that vitamin B6 deficiency-induced gestational glucose intolerance involves additional mechanisms that are complex and insulin independent.

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Constitutive Activity of Serotonin Receptor 6 Regulates Human Cerebral Organoids Formation and Depression-like Behaviors

Stem Cell Reports ◽

10.1016/j.stemcr.2020.11.015 ◽

2020 ◽

Author(s):

Qinying Wang ◽

Xiaoxu Dong ◽

Tingting Hu ◽

Chao Qu ◽

Jing Lu ◽

...

Keyword(s):

Serotonin Receptor ◽

Constitutive Activity

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Living-Cell Diffracted X-ray Tracking Analysis Confirmed Internal Salt Bridge Is Critical for Ligand-Induced Twisting Motion of Serotonin Receptors

International Journal of Molecular Sciences ◽

10.3390/ijms22105285 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5285

Author(s):

Kazuhiro Mio ◽

Shoko Fujimura ◽

Masaki Ishihara ◽

Masahiro Kuramochi ◽

Hiroshi Sekiguchi ◽

...

Keyword(s):

Serotonin Receptors ◽

Serotonin Receptor ◽

Frame Rate ◽

Receptor Subtype ◽

Transmembrane Segment ◽

Hek 293 ◽

Gold Nanocrystals ◽

X Ray ◽

Time Dynamics ◽

Analytical Technique

Serotonin receptors play important roles in neuronal excitation, emotion, platelet aggregation, and vasoconstriction. The serotonin receptor subtype 2A (5-HT2AR) is a Gq-coupled GPCR, which activate phospholipase C. Although the structures and functions of 5-HT2ARs have been well studied, little has been known about their real-time dynamics. In this study, we analyzed the intramolecular motion of the 5-HT2AR in living cells using the diffracted X-ray tracking (DXT) technique. The DXT is a very precise single-molecular analytical technique, which tracks diffraction spots from the gold nanocrystals labeled on the protein surface. Trajectory analysis provides insight into protein dynamics. The 5-HT2ARs were transiently expressed in HEK 293 cells, and the gold nanocrystals were attached to the N-terminal introduced FLAG-tag via anti-FLAG antibodies. The motions were recorded with a frame rate of 100 μs per frame. A lifetime filtering technique demonstrated that the unliganded receptors contain high mobility population with clockwise twisting. This rotation was, however, abolished by either a full agonist α-methylserotonin or an inverse agonist ketanserin. Mutation analysis revealed that the “ionic lock” between the DRY motif in the third transmembrane segment and a negatively charged residue of the sixth transmembrane segment is essential for the torsional motion at the N-terminus of the receptor.

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An approach for serotonin depletion in pigs: Effects on serotonin receptor binding

Synapse ◽

10.1002/syn.20827 ◽

2010 ◽

Vol 65 (2) ◽

pp. 136-145 ◽

Cited By ~ 15

Author(s):

Anders Ettrup ◽

Birgitte R. Kornum ◽

Pia Weikop ◽

Gitte M. Knudsen

Keyword(s):

Receptor Binding ◽

Serotonin Receptor ◽

Serotonin Depletion ◽

Serotonin Receptor Binding

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Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease

Viruses ◽

10.3390/v13081540 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1540

Author(s):

Beatriz Sierra ◽

Ana Cristina Magalhães ◽

Daniel Soares ◽

Bruno Cavadas ◽

Ana B. Perez ◽

...

Keyword(s):

Receptor Antagonist ◽

Dengue Fever ◽

In Silico ◽

Serotonin Receptor ◽

Neglected Tropical Diseases ◽

Dengue Infection ◽

Severe Dengue ◽

Functional Evaluation ◽

Atpase Inhibitor ◽

Serotonin Receptor Antagonist

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico–informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, “Adrenergic receptor antagonist”, “ATPase inhibitor”, “NF-kB pathway inhibitor” and “Serotonin receptor antagonist”, were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.

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Molecular Cloning and Functional Characterization of Three 5-HT Receptor Genes (HTR1B, HTR1E and HTR1F) in Chickens

Genes ◽

10.3390/genes12060891 ◽

2021 ◽

Vol 12 (6) ◽

pp. 891

Author(s):

Caiyun Sun ◽

Yang Qiu ◽

Qin Ren ◽

Xiao Zhang ◽

Baolong Cao ◽

...

Keyword(s):

Serotonin Receptor ◽

Functional Characterization ◽

Brain Regions ◽

Luciferase Reporter ◽

Molecular Characteristics ◽

Intracellular Camp ◽

Pituitary Cells ◽

Dependent Manner ◽

Serotonin Signaling ◽

Reporter Assays

The serotonin (5-hydroxytryptamine, 5-HT) signaling system is involved in a variety of physiological functions, including the control of cognition, reward, learning, memory, and vasoconstriction in vertebrates. Contrary to the extensive studies in the mammalian system, little is known about the molecular characteristics of the avian serotonin signaling network. In this study, we cloned and characterized the full-length cDNA of three serotonin receptor genes (HTR1B, HTR1E and HTR1F) in chicken pituitaries. Synteny analyses indicated that HTR1B, HTR1E and HTR1F were highly conserved across vertebrates. Cell-based luciferase reporter assays showed that the three chicken HTRs were functional, capable of binding their natural ligands (5-HT) or selective agonists (CP94253, BRL54443, and LY344864) and inhibiting intracellular cAMP production in a dose-dependent manner. Moreover, activation of these receptors could stimulate the MAPK/ERK signaling cascade. Quantitative real-time PCR analyses revealed that HTR1B, HTR1E and HTR1F were primarily expressed in various brain regions and the pituitary. In cultured chicken pituitary cells, we found that LY344864 could significantly inhibit the secretion of PRL stimulated by vasoactive intestinal peptide (VIP) or forskolin, revealing that HTR1F might be involved in the release of prolactin in chicken. Our findings provide insights into the molecular mechanism and facilitate a better understanding of the serotonergic modulation via HTR1B, HTR1E and HTR1F in avian species.

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