6,468 research outputs found
5-hydroxytryptamine (5-HT) cellular sequestration during chronic exposure delays 5-HT<sub>3</sub> receptor resensitization due to Its subsequent release
No full textThe serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT3) receptors. We report that recombinantly expressed 5-HT3 receptor binding sites are reduced by chronic exposure to 5-HT (IC50 of 154.0 ± 45.7 μm, t½ = 28.6 min). This is confirmed for 5-HT3 receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC50 of 2.3 ± 1.0 μm, t½ = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization
5-ht inhibition of rat insulin 2 promoter cre recombinase transgene and proopiomelanocortin neuron excitability in the mouse arcuate nucleus
No full textA number of anti-obesity agents have been developed that enhance hypothalamic 5-HT transmission. Various studies have demonstrated that arcuate neurons, which express proopiomelanocortin peptides (POMC neurons), and neuropeptide Y with agouti-related protein (NPY/AgRP) neurons, are components of the hypothalamic circuits responsible for energy homeostasis. An additional arcuate neuron population, rat insulin 2 promoter Cre recombinase transgene (RIPCre) neurons, has recently been implicated in hypothalamic melanocortin circuits involved in energy balance. It is currently unclear how 5-HT modifies neuron excitability in these local arcuate neuronal circuits. We show that 5-HT alters the excitability of the majority of mouse arcuate RIPCre neurons, by either hyperpolarization and inhibition or depolarization and excitation. RIPCre neurons sensitive to 5-HT, predominantly exhibit hyperpolarization and pharmacological studies indicate that inhibition of neuronal firing is likely to be through 5-HT1F receptors increasing current through a voltage-dependent potassium conductance. Indeed, 5-HT1F receptor immunoreactivity co-localizes with RIPCre green fluorescent protein expression. A minority population of POMC neurons also respond to 5-HT by hyperpolarization, and this appears to be mediated by the same receptor-channel mechanism. As neither POMC nor RIPCre neuronal populations display a common electrical response to 5-HT, this may indicate that sub-divisions of POMC and RIPCre neurons exist, perhaps serving different outputs. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.</p
Youthhood
No full textTESTING-GROUND issue 03, Youthhood, examines worlds through youthful eyes, makes evident young ambitions, and questions how we can better empower young people to design cities, landscapes, and a planet that works for them. The issue includes contributions from: Carmel Keren, Jude Daniel Smith, Claire Edwards, Kazeem Kuteyi, Emmanuel Adarkwah, Reza Nik, Dan Cui, Kristofer Cullum-Fernandez, Fida Sassi, Simeon Shtebunaev, Daze Aghaji, Averill Dimabuyu, Sarri Elfaitouri, Rebecca McDonald-Balfour, and Ed Wall.
Rebecca McDonald-Balfour (Author), Jude Daniel Smith (Author), Daze Aghaji (Author), Carmel Keran (Author), Alexis Liu (Author), Dan Cui (Author), Kristofer Cullum-Fernandez (Author), Fida Sassi (Author), Averill Dimabuyu (Author), Ed
Inhibition of native 5-HT3 receptor-evoked contractions in Guinea pig and mouse ileum by antimalarial drugs
No full textQuinine, Chloroquine and mefloquine are commonly used to treat malaria; however with associated gastrointestinal (GI) side-effects. These drugs act as antagonists at recombinant 5-HT3 receptors and modulate gut peristalsis. These gastrointestinal side effects may be the result of antagonism at intestinal 5-HT3 receptors. Ileum from male C57BL/6 mice and guinea pigs was mounted longitudinally in organ baths. Concentration-response curves for 5-HT and the selective 5-HT3 agonist 2-Me-5-HT were obtained with 5-HT (pEC50=7.57±0.33, 12) more potent (P=0.004) than 2-Me-5-HT (pEC50=5.45±0.58, n=5) in mouse ileum. There was no difference in potency of 5-HT (pEC50=5.42±0.15, n=8) and 2-Me-5-HT (pIC50=5.01±0.55, n=11) in guinea pig ileum (P>0.05). Quinine, Chloroquine or mefloquine was applied for 10 min and inhibitions prior to submaximal agonist application. In mouse ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions (pIC50=4.9±0.17, n=7; 4.76±0.14,n=5; 6.21±0.2, n=4, respectively) with mefloquine most potent (P<0.05). Quinine, chloroquine and mefloquine antagonised 2-me-5-HT-induced contractions (pIC50=6.35±0.11,n=8; 4.64±0.2, n=7; 5.11± 0.22, n=6, respectively) with quinine most potent (P<0.05). In guinea-pig ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions (pIC50=5.02±0.15, n=6; 4.54±0.1, n=7; 5.32±0.13, n=5, respectively) and 2-me-5-HT-induced contractions (pIC50=4.62±0.25, n=5; 4.56±0.14, n=6; 5.67±0.12, n=4, respectively) with chloroquine least potent against 5-HT and mefloquine most potent against 2-me-5-HT (P<0.05). These results support previous studies identifying anti-malarial drugs as antagonists at recombinant 5-HT3 receptors and may also demonstrate the ability of these drugs to influence native 5-HT3 receptor-evoked contractile responses which may account for their associated GI side-effects
Genotyping the clonal structure of a gorgonian coral, Juncella juncea (Anthozoa: Octocorallia), using microsatellite loci.
No full textQuality of Life of Patients with Gastric Cancer in Taiwan: Validation and Clinical Application of the Taiwan Chinese Version of the EORTC QLQ-C30 and EORTC QLQ-STO22.
No full textEnantioseparation of phenothiazines in cyclodextrin-modified capillary zone electrophoresis using sulfated cyclodextrins as chiral selectors
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The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine
No full textBackground: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT.
Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine.
Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists.
Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum.
Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions.
Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal
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