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Tetrodotoxin

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https://www.readbyqxmd.com/read/28533144/discovery-of-two-p-superfamily-conotoxins-lt9a-and-lt9b-with-different-modifications-on-voltage-sensitive-sodium-channels
#1
Lei Wang, Junliang Liu, Zhenghua Ren, Yu Chen, Anlong Xu
In this work, two P-superfamily conotoxins, lt9a and lt9b, were purified and characterized from the crude venom of Conus litteratus. The amino acid sequences of lt9a and lt9b were determined by the Edman degradation method. It has been suggested that both lt9a and lt9b are produced from the precursor encoded by the gene Lt9.1. During the conotoxin maturation process, different post-translational modifications occurred between lt9a and lt9b. Conotoxin lt9b was predicted to have two prolines that underwent hydroxylation and one glutamate that underwent carboxylation, while lt9a had no hydroxyproline and carboxyglutamate residue...
May 19, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28529474/mir-30b-attenuates-neuropathic-pain-by-regulating-voltage-gated-sodium-channel-nav1-3-in-rats
#2
Songxue Su, Jinping Shao, Qingzan Zhao, Xiuhua Ren, Weihua Cai, Lei Li, Qian Bai, Xuemei Chen, Bo Xu, Jian Wang, Jing Cao, Weidong Zang
Nav1.3 is a tetrodotoxin-sensitive isoform among voltage-gated sodium channels that are closely associated with neuropathic pain. It can be up-regulated following nerve injury, but its biological function remains uncertain. MicroRNAs (miRNAs) are endogenous non-coding RNAs that can regulate post-transcriptional gene expression by binding with their target mRNAs. Using Target Scan software, we discovered that SCN3A is the major target of miR-30b, and we then determined whether miR-30b regulated the expression of Nav1...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28528177/tetrodotoxin-in-asian-newts-salamandridae
#3
Mari Yotsu-Yamashita, Stefan W Toennes, Dietrich Mebs
Tetrodotoxin (TTX) and its analogues occur in a wide range of marine animals but also in terrestrial vertebrates such as frogs, toads and newts. Despite numerous studies on TTX in New World newts (Notophthalmus viridescens, Taricha spp.), few data only exist for Asian newts. Methanolic extracts of newts from China (Cynops orientalis, Pachytriton labiatus, Paramesotriton chinensis), Vietnam (Paramesotriton deloustali, P. guangxiensis), and Laos (Laotriton laoensis) were analyzed by liquid-chromatography-fluorescent detection (LC-FLD) and mass-spectrometry (LC-MS)...
May 17, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28527717/inhibition-of-the-lateral-habenular-camk%C3%A2-abolishes-naloxone-precipitated-conditioned-place-aversion-in-morphine-dependent-mice
#4
Jing Wang, Min Li, Ping Wang, Yunhong Zha, Zhi He, Zicheng Li
Addictive substances mediate positive and negative states promoting compulsive drug use. However, substrates for aversive effects of drugs are not fully understood. We found that inactivation of the lateral habenula (LHb) by microinjection of tetrodotoxin (TTX) abolished naloxone-precipitated conditioned place aversion (CPA) in morphine-dependent mice. We also found that lateral habenular administration of KN-62, a specific inhibitor for calcium/calmodulin dependent protein kinase II (CaMKII), abolished naloxone-precipitated CPA in morphine-dependent mice...
May 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28522210/novel-trigeminal-slice-preparation-method-for-studying-mechanisms-of-nociception-transmission
#5
Mikiko Hirahara, Naoshi Fujiwara, Kenji Seo
BACKGROUND: The trigeminal subnucleus caudalis (Vc) plays a critical role in transmission and modulation of nociceptive afferent inputs, and exhibits a similar layer construction to the spinal dorsal horn. However, afferent inputs enter the brainstem and project to a separately located nucleus. It has previously been difficult to record responses of the Vc to afferent fiber activation in a brainstem slice preparation. The aim of the present study was to establish a novel brainstem slice preparation method to study trigeminal nociceptive transmission mechanisms...
May 15, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28513564/tetrodotoxin-producing-bacteria-detection-distribution-and-migration-of-the-toxin-in-aquatic-systems
#6
REVIEW
Timur Yu Magarlamov, Daria I Melnikova, Alexey V Chernyshev
This review is devoted to the marine bacterial producers of tetrodotoxin (TTX), a potent non-protein neuroparalytic toxin. In addition to the issues of the ecology and distribution of TTX-producing bacteria, this review examines issues relating to toxin migration from bacteria to TTX-bearing animals. It is shown that the mechanism of TTX extraction from toxin-producing bacteria to the environment occur through cell death, passive/active toxin excretion, or spore germination of spore-forming bacteria. Data on TTX microdistribution in toxic organs of TTX-bearing animals indicate toxin migration from the digestive system to target organs through the transport system of the organism...
May 17, 2017: Toxins
https://www.readbyqxmd.com/read/28511871/effect-of-distigmine-on-the-contractile-response-of-guinea-pig-urinary-bladder-to-electrical-field-stimulation
#7
Keisuke Obara, Yurina Kobayashi, Daisuke Chino, Yoshio Tanaka
Distigmine bromide (distigmine) is a reversible carbamate group cholinesterase (ChE) inhibitor. Although mainly used clinically for the treatment of myasthenia gravis, distigmine is also indicated for detrusor underactivity in Japan. According to the pharmacological classification of distigmine, its therapeutic effect against detrusor underactivity appears to be produced by enhanced urinary bladder smooth muscle (UBSM) contractility due to an increased concentration of acetylcholine between parasympathetic nerve endings and UBSM cells...
May 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28508747/voltage-gated-na-currents-in-human-dorsal-root-ganglion-neurons
#8
Xiulin Zhang, Birgit T Priest, Inna Belfer, Michael S Gold
Available evidence indicates voltage-gated Na(+) channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of the biophysical and pharmacological properties of the channels in sensory neurons is largely based on the study of heterologous systems or rodent tissue, despite evidence that both expression systems and species differences influence these properties. Therefore, we sought to determine the extent to which the biophysical and pharmacological properties of VGSCs were comparable in rat and human sensory neurons...
May 16, 2017: ELife
https://www.readbyqxmd.com/read/28499975/intracortical-signal-processing-of-periodontal-ligament-sensations-in-rat
#9
Aoi Minoda, Naoko Mizoguchi, Masayuki Kobayashi, Naoto Suda, Kazuyo Muramoto
The somatosensory information from the orofacial region, including the periodontal ligament (PDL), is processed in a manner that differs from that used for other body somatosensory information in the related cortices. It was reported that electrical stimulation to rat PDL elicited activation of the insular oral region (IOR) and the primary (S1) and secondary (S2) somatosensory cortices. However, the physiological relationship between S1 and S2/IOR is not well understood. To address this issue, we performed in vivo optical imaging using a voltage-sensitive dye...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28499969/corticotropin-releasing-hormone-modulates-airway-vagal-preganglionic-neurons-of-sprague-dawley-rats-at-multiple-synaptic-sites-via-activation-of-its-type-1-receptors-implications-for-stress-associated-airway-vagal-excitation
#10
Yuhong Guo, Xianxia Yan, Xingxin Chen, Ding He, Ming Zeng, Yonghua Chen, Chunmei Xia, Dongying Qiu, Jijiang Wang
Corticotropin-releasing hormone release is the final common pathway of stress-associated neuroendocrine responses. This study tested how corticotropin-releasing hormone modulates airway vagal preganglionic neurons. Airway vagal preganglionic neurons in neonatal rats were retrogradely labeled with fluorescent dye and identified in medullary slices, and their responses to corticotropin-releasing hormone (200nmolL(-1)) were examined using whole-cell patch clamp. The results show that under current clamp, corticotropin-releasing hormone (200nmolL(-1)) depolarized airway vagal preganglionic neurons and significantly increased the rate of their spontaneous firing...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28496413/cholera-toxin-induces-sustained-hyperexcitability-in-myenteric-but-not-submucosal-ah-neurons-in-guinea-pig-jejunum
#11
Katerina Koussoulas, Rachel M Gwynne, Jaime P P Foong, Joel C Bornstein
Background and Aims: Cholera toxin (CT)-induced hypersecretion requires activation of secretomotor pathways in the enteric nervous system (ENS). AH neurons, which have been identified as a population of intrinsic sensory neurons (ISNs), are a source of excitatory input to the secretomotor pathways. We therefore examined effects of CT in the intestinal lumen on myenteric and submucosal AH neurons. Methods: Isolated segments of guinea pig jejunum were incubated for 90 min with saline plus CT (12.5 μg/ml) or CT + neurotransmitter antagonist, or CT + tetrodotoxin (TTX) in their lumen...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28487635/vpac-receptor-subtypes-tune-purinergic-neuron-to-glia-communication-in-the-murine-submucosal-plexus
#12
Candice Fung, Werend Boesmans, Carla Cirillo, Jaime P P Foong, Joel C Bornstein, Pieter Vanden Berghe
The enteric nervous system (ENS) situated within the gastrointestinal tract comprises an intricate network of neurons and glia which together regulate intestinal function. The exact neuro-glial circuitry and the signaling molecules involved are yet to be fully elucidated. Vasoactive intestinal peptide (VIP) is one of the main neurotransmitters in the gut, and is important for regulating intestinal secretion and motility. However, the role of VIP and its VPAC receptors within the enteric circuitry is not well understood...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28482835/mechanism-of-resveratrol-induced-relaxation-in-the-human-gallbladder
#13
Ching-Chung Tsai, Ming-Che Lee, Shu-Leei Tey, Ching-Wen Liu, Shih-Che Huang
BACKGROUND: Resveratrol is a polyphenolic compound extracted from plants and is also a constituent of red wine. Resveratrol produces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Although resveratrol has been reported to cause relaxation of the guinea pig gallbladder, limited data are available about the effect of resveratrol on the gallbladder smooth muscle in humans. The purpose of this study was to investigate the relaxation effects of resveratrol in human gallbladder muscle strips...
May 8, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28473457/pharmacologic-characterization-of-amg8379-a-potent-and-selective-small-molecule-sulfonamide-antagonist-of-the-voltage-gated-sodium-channel-nav1-7
#14
Thomas J Kornecook, Ruoyuan Yin, Stephen Altmann, Xuhai Be, Virginia Berry, Christopher P Ilch, Michael Jarosh, Danielle Johnson, Josie H Lee, Sonya G Lehto, Joseph Ligutti, Dong Liu, Jason Luther, David Matson, Danny Ortuno, John Roberts, Kristin Taborn, Jinti Wang, Matthew M Weiss, Violeta Yu, Dawn X D Zhu, Robert T Fremeau, Bryan D Moyer
Potent and selective antagonists of the voltage-gated sodium channel NaV1.7 represent a promising avenue for the development of new chronic pain therapies. We generated a small molecule atropisomer quinolone sulfonamide antagonist AMG8379 and a less active enantiomer AMG8380. Here we show that AMG8379 potently blocks human NaV1.7 channels with an IC50 of 8.5 nM and endogenous tetrodotoxin (TTX)-sensitive sodium channels in dorsal root ganglia (DRG) neurons with an IC50 of 3.1 nM in whole cell patch clamp electrophysiology assays using a voltage protocol that interrogates channels in a partially inactivated state...
May 4, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28452816/tetrodotoxin-epinephrine-and-chemical-permeation-enhancer-combinations-in-peripheral-nerve-blockade
#15
Claudia M Santamaria, Changyou Zhan, J Brian McAlvin, David Zurakowski, Daniel S Kohane
BACKGROUND: Chemical permeation enhancers (CPEs) have the potential to improve nerve blockade by site 1 sodium channel blockers such as tetrodotoxin (TTX). Here, we investigated the efficacy and toxicity of CPE-enhanced nerve blockade across a range of TTX concentrations using 2 CPEs (sodium octyl sulfate and octyl trimethyl ammonium bromide). We also tested the hypothesis that CPEs could be used to reduce the concentrations of TTX and/or of a second adjuvant drug (in this case, epinephrine) needed to achieve prolonged local anesthesia METHODS:: Sprague-Dawley rats were injected at the sciatic nerve with combinations of TTX and CPEs, with and without epinephrine...
June 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28450535/sodium-channel-nav1-8-underlies-ttx-resistant-axonal-action-potential-conduction-in-somatosensory-c-fibers-of-distal-cutaneous-nerves
#16
Amanda H Klein, Alina Vyshnevska, Timothy V Hartke, Roberto De Col, Joseph L Mankowski, Brian Turnquist, Frank Bosmans, Peter W Reeh, Martin Schmelz, Richard W Carr, Matthias Ringkamp
Voltage-gated sodium (NaV) channels are responsible for the initiation and conduction of action potentials within primary afferents. The nine NaV channel isoforms recognized in mammals are often functionally divided into tetrodotoxin (TTX)-sensitive (TTX-s) channels (NaV1.1-NaV1.4, NaV1.6-NaV1.7) that are blocked by nanomolar concentrations and TTX-resistant (TTX-r) channels (NaV1.8 and NaV1.9) inhibited by millimolar concentrations, with NaV1.5 having an intermediate toxin sensitivity. For small-diameter primary afferent neurons, it is unclear to what extent different NaV channel isoforms are distributed along the peripheral and central branches of their bifurcated axons...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28444988/inhibitory-action-of-oxytocin-on-spontaneous-contraction-of-rat-distal-colon-by-nitrergic-mechanism-involvement-of-cyclic-gmp-and-apamin-sensitive-k-channels
#17
R Wang, M T Han, X L Lv, Y A Yu, S Q Chai, C M Qu, C Y Liu
AIM: The mechanisms underlying the inhibitory effects of oxytocin (OT) on colon tone are not totally understood. We explore the mechanisms of OT on spontaneous contractility in rat distal colon and identify the mediators involved in this action. METHODS: In rat distal colon strips, mechanical activity was analysed and the production of nitric oxide (NO) in tissue loaded with the fluorochrome DAF-FM was visualized by confocal microscopy. OT receptor (OTR) expression was determined by Western blotting and immunofluorescence...
April 26, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28444866/new-insights-into-neurogenic-cyclic-motor-activity-in-the-isolated-guinea-pig-colon
#18
M Costa, L Wiklendt, L Keightley, S J H Brookes, P G Dinning, N J Spencer
BACKGROUND: The contents of the guinea pig distal colon consist of multiple pellets that move anally in a coordinated manner. This row of pellets results in continued distention of the colon. In this study, we have investigated quantitatively the features of the neurally dependent colonic motor patterns that are evoked by constant distension of the full length of guinea-pig colon. METHODS: Constant distension was applied to the excised guinea-pig by high-resolution manometry catheters or by a series of hooks...
April 26, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28442111/toxicity-assessment-and-screening-of-tetrodotoxin-in-the-oblong-blowfish-takifugu-oblongus-from-the-tamil-nadu-coast-of-bay-of-bengal-india
#19
S M Indumathi, S S Khora
OBJECTIVE: To assess the toxicity of the pufferfish Takifugu oblongus, from Chennai coast, Tamil Nadu, India and to detect the presence of Tetrodotoxin (TTX). METHODS: The toxicity was evaluated by mouse bioassay using Swiss Albino mice which were expressed in mouse units (MU). Gross anatomical features were observed which is followed by histopathology of the dead mice tissues to establish the toxicity. Instrumental analysis for the presence of tetrodotoxin was also performed through GC-MS and HPLC...
March 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28440808/automated-and-manual-patch-clamp-data-of-human-induced-pluripotent-stem-cell-derived-dopaminergic-neurons
#20
Denise Franz, Hervør Lykke Olsen, Oliver Klink, Jan Gimsa
Human induced pluripotent stem cells can be differentiated into dopaminergic neurons (Dopa.4U). Dopa.4U neurons expressed voltage-gated NaV and KV channels and showed neuron-like spontaneous electrical activity. In automated patch clamp measurements with suspended Dopa.4U neurons, delayed rectifier K(+) current (delayed KV) and rapidly inactivating A-type K(+) current (fast KV) were identified. Examination of the fast KV current with inhibitors yielded IC50 values of 0.4 mM (4-aminopyridine) and 0.1 mM (tetraethylammonium)...
April 25, 2017: Scientific Data
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