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T-type calcium channels antagonists

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https://www.readbyqxmd.com/read/27902567/dorsal-root-ganglion-neurons-become-hyperexcitable-and-increase-expression-of-voltage-gated-t-type-calcium-channels-cav3-2-in-paclitaxel-induced-peripheral-neuropathy
#1
Yan Li, Claudio Esteves Tatsui, Laurence D Rhines, Robert Y North, Daniel S Harrison, Ryan M Cassidy, Caj A Johansson, Alyssa K Kosturakis, Denaya D Edwards, Hongmei Zhang, Patrick M Dougherty
Here it is shown that paclitaxel induced neuropathy is associated with the development of spontaneous activity (SA) and hyperexcitability in DRG neurons that is paralleled by increased expression of low-voltage-activated calcium channels (T-type; Cav3.2). The percentage of DRG neurons showing SA and the overall mean rate of SA were significantly higher at day 7 of paclitaxel treatment than in rats receiving vehicle. Cav3.2 expression was increased in L4-6 DRG and spinal cord segments in paclitaxel-treated rats, localized to small calcitonin gene-related peptide expressing and isolectin B4 expressing DRG neurons and to glial fibrillary acidic protein-positive spinal cord cells...
November 24, 2016: Pain
https://www.readbyqxmd.com/read/27759880/ph%C3%AE-1%C3%AE-acts-as-a-trpa1-antagonist-with-antinociceptive-effects-in-mice
#2
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27596273/lack-of-antiparkinsonian-effects-of-systemic-injections-of-the-specific-t-type-calcium-channel-blocker-ml218-in-mptp-treated-monkeys
#3
Adriana Galvan, Annaelle Devergnas, Damien Pittard, Gunasingh Masilamoni, Jocelyn Vuong, J Scott Daniels, Ryan D Morrison, Craig W Lindsley, Thomas Wichmann
Dopaminergic medications ameliorate many of the motor impairments of Parkinson's disease (PD). However, parkinsonism is often only partially reversed by these drugs, and they can have significant side effects. Therefore, a need remains for novel treatments of parkinsonism. Studies in rodents and preliminary clinical evidence have shown that T-type calcium channel (TTCC) antagonists have antiparkinsonian effects. However, most of the available studies utilized nonselective agents. We now evaluated whether systemic injections of the specific TTCC blocker ML218 have antiparkinsonian effects in MPTP-treated parkinsonian Rhesus monkeys...
September 20, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27439609/anti-nociceptive-and-desensitizing-effects-of-olvanil-on-capsaicin-induced-thermal-hyperalgesia-in-the-rat
#4
Mohammad Alsalem, Paul Millns, Ahmad Altarifi, Khalid El-Salem, Victoria Chapman, David A Kendall
BACKGROUND: Olvanil (NE 19550) is a non-pungent synthetic analogue of capsaicin, the natural pungent ingredient of capsicum which activates the transient receptor potential vanilloid type-1 (TRPV1) channel and was developed as a potential analgesic compound. Olvanil has potent anti-hyperalgesic effects in several experimental models of chronic pain. Here we report the inhibitory effects of olvanil on nociceptive processing using cultured dorsal root ganglion (DRG) neurons and compare the effects of capsaicin and olvanil on thermal nociceptive processing in vivo; potential contributions of the cannabinoid CB1 receptor to olvanil's anti-hyperalgesic effects were also investigated...
2016: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27365170/the-t-type-calcium-channel-antagonist-z944-disrupts-prepulse-inhibition-in-both-epileptic-and-non-epileptic-rats
#5
Wendie N Marks, Quentin Greba, Stuart M Cain, Terrance P Snutch, John G Howland
The role of T-type calcium channels in brain diseases such as absence epilepsy and neuropathic pain has been studied extensively. However, less is known regarding the involvement of T-type channels in cognition and behavior. Prepulse inhibition (PPI) is a measure of sensorimotor gating which is a basic process whereby the brain filters incoming stimuli to enable appropriate responding in sensory rich environments. The regulation of PPI involves a network of limbic, cortical, striatal, pallidal and pontine brain areas, many of which show high levels of T-type calcium channel expression...
September 22, 2016: Neuroscience
https://www.readbyqxmd.com/read/27353765/growth-differentiation-factor-15-promotes-glutamate-release-in-medial-prefrontal-cortex-of-mice-through-upregulation-of-t-type-calcium-channels
#6
Dong-Dong Liu, Jun-Mei Lu, Qian-Ru Zhao, Changlong Hu, Yan-Ai Mei
Growth differentiation factor-15 (GDF-15) has been implicated in ischemic brain injury and synapse development, but its involvement in modulating neuronal excitability and synaptic transmission remain poorly understood. In this study, we investigated the effects of GDF-15 on non-evoked miniature excitatory post-synaptic currents (mEPSCs) and neurotransmitter release in the medial prefrontal cortex (mPFC) in mice. Incubation of mPFC slices with GDF-15 for 60 min significantly increased the frequency of mEPSCs without effect on their amplitude...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27282256/the-t-type-calcium-channel-antagonist-z944-rescues-impairments-in-crossmodal-and-visual-recognition-memory-in-genetic-absence-epilepsy-rats-from-strasbourg
#7
Wendie N Marks, Stuart M Cain, Terrance P Snutch, John G Howland
Childhood absence epilepsy (CAE) is often comorbid with behavioral and cognitive symptoms, including impaired visual memory. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is an animal model closely resembling CAE; however, cognition in GAERS is poorly understood. Crossmodal object recognition (CMOR) is a recently developed memory task that examines not only purely visual and tactile memory, but also requires rodents to integrate sensory information about objects gained from tactile exploration to enable visual recognition...
October 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27273014/p-q-type-and-t-type-voltage-gated-calcium-channels-are-involved-in-the-contraction-of-mammary-and-brain-blood-vessels-from-hypertensive-patients
#8
Anne D Thuesen, Kristina S Lyngsø, Lotte Rasmussen, Jane Stubbe, Ole Skøtt, Frantz R Poulsen, Christian Bonde Pedersen, Lars M Rasmussen, Pernille B L Hansen
AIM: Calcium channel blockers are widely used in cardiovascular diseases. Beside L-type channels, T- and P/Q-type calcium channels are involved in contraction of human renal blood vessels. It was hypothesized that T- and P/Q -type channels are involved in contraction of human brain and mammary blood vessels. METHODS: Internal mammary arteries from bypass surgery patients and cerebral arterioles from patients with brain tumors with and with-out hypertension were tested in a myograph and perfusion set-up...
June 7, 2016: Acta Physiologica
https://www.readbyqxmd.com/read/27242667/t-type-calcium-channel-a-privileged-gate-for-calcium-entry-and-control-of-adrenal-steroidogenesis
#9
REVIEW
Michel F Rossier
Intracellular calcium plays a crucial role in modulating a variety of functions such as muscle contraction, hormone secretion, gene expression, or cell growth. Calcium signaling has been however shown to be more complex than initially thought. Indeed, it is confined within cell microdomains, and different calcium channels are associated with different functions, as shown by various channelopathies. Sporadic mutations on voltage-operated L-type calcium channels in adrenal glomerulosa cells have been shown recently to be the second most prevalent genetic abnormalities present in human aldosterone-producing adenoma...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27240535/a-systematic-review-of-calcium-channel-antagonists-in-bipolar-disorder-and-some-considerations-for-their-future-development
#10
A Cipriani, K Saunders, M-J Attenburrow, J Stefaniak, P Panchal, S Stockton, T A Lane, E M Tunbridge, J R Geddes, P J Harrison
l-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this class of drugs has been rekindled by the discovery that LTCC genes are part of the genetic aetiology of bipolar disorder and related phenotypes. We have therefore conducted a systematic review of LTCC antagonists in the treatment and prophylaxis of bipolar disorder. We identified 23 eligible studies, with six randomised, double-blind, controlled clinical trials, all of which investigated verapamil in acute mania, and finding no evidence that it is effective...
October 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27146976/the-transcription-factor-neurod2-coordinates-synaptic-innervation-and-cell-intrinsic-properties-to-control-excitability-of-cortical-pyramidal-neurons
#11
Fading Chen, Jacqueline T Moran, Yihui Zhang, Kristin M Ates, Diankun Yu, Laura A Schrader, Partha M Das, Frank E Jones, Benjamin J Hall
KEY POINTS: Synaptic excitation and inhibition must be properly balanced in individual neurons and neuronal networks to allow proper brain function. Disrupting this balance may lead to autism spectral disorders and epilepsy. We show the basic helix-loop-helix transcription factor NeuroD2 promotes inhibitory synaptic drive but also decreases cell-intrinsic neuronal excitability of cortical pyramidal neurons both in vitro and in vivo. We identify two genes potentially downstream of NeuroD2-mediated transcription that regulate these parameters: gastrin-releasing peptide and the small conductance, calcium-activated potassium channel, SK2...
July 1, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27025064/signal-mediators-at-induction-of-heat-resistance-of-wheat-plantlets-by-short-term-heating
#12
Yu V Karpets, Yu E Kolupaev, T O Yastreb
The effects of functional interplay of calcium ions, reactive oxygen species (ROS) and nitric oxide (NO) in the cells of wheat plantlets roots (Triticum aestivum L.) at the induction of their heat resistance by a short-term influence of hyperthermia (heating at the temperature of 42 degrees C during 1 minute) have been investigated. The transitional increase of NO and H2O2 content, invoked by heating, was suppressed by the treatment of plantlets with the antagonists of calcium EGTA (chelator of exocellular calcium), lanthanum chloride (blocker of calcium channels of various types) and neomycin (inhibitor of phosphatidylinositol-dependent phospholipase C)...
November 2015: Ukrainian Biochemical Journal
https://www.readbyqxmd.com/read/27022465/activation-of-transient-receptor-potential-ankyrin-1-induces-cgrp-release-from-spinal-cord-synaptosomes
#13
Talisia Quallo, Clive Gentry, Stuart Bevan, Lisa M Broad, Adrian J Mogg
Transient receptor potential ankyrin 1 (TRPA1) is a sensor of nociceptive stimuli, expressed predominantly in a subpopulation of peptidergic sensory neurons which co-express the noxious heat-sensor transient receptor potential vanilloid 1. In this study, we describe a spinal cord synaptosome-calcitonin gene-related peptide (CGRP) release assay for examining activation of TRPA1 natively expressed on the central terminals of dorsal root ganglion neurons. We have shown for the first time that activation of TRPA1 channels expressed on spinal cord synaptosomes by a selection of agonists evokes a concentration-dependent release of CGRP which is inhibited by TRPA1 antagonists...
December 2015: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/27006502/differential-volume-regulation-and-calcium-signaling-in-two-ciliary-body-cell-types-is-subserved-by-trpv4-channels
#14
Andrew O Jo, Monika Lakk, Amber M Frye, Tam T T Phuong, Sarah N Redmon, Robin Roberts, Bruce A Berkowitz, Oleg Yarishkin, David Križaj
Fluid secretion by the ciliary body plays a critical and irreplaceable function in vertebrate vision by providing nutritive support to the cornea and lens, and by maintaining intraocular pressure. Here, we identify TRPV4 (transient receptor potential vanilloid isoform 4) channels as key osmosensors in nonpigmented epithelial (NPE) cells of the mouse ciliary body. Hypotonic swelling and the selective agonist GSK1016790A (EC50 ∼33 nM) induced sustained transmembrane cation currents and cytosolic [Formula: see text] elevations in dissociated and intact NPE cells...
April 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26875775/progesterone-suppressed-vasoconstriction-in-human-umbilical-vein-via-reducing-calcium-entry
#15
Yun He, Qinqin Gao, Bing Han, Xiaolin Zhu, Di Zhu, Jianying Tao, Jie Chen, Zhice Xu
The aim of this study was to evaluate the actions of progesterone on human umbilical vein (HUV) from normal pregnancies and the possible underlying mechanisms involved. HUV rings were suspended in organ baths and exposed to progesterone followed by phenylephrine (PE) or serotonin (5-HT). Progesterone suppressed PE- or 5-HT-induced vasoconstriction in HUV rings. The inhibitory effect induced by progesterone was not influenced by nitric oxide syntheses inhibitor, prostaglandins syntheses blocker, the integrity of endothelium, selective progesterone receptor or potassium channel antagonists...
April 2016: Steroids
https://www.readbyqxmd.com/read/26854031/synergism-of-perampanel-and-zonisamide-in-the-rat-amygdala-kindling-model-of-temporal-lobe-epilepsy
#16
Vera Russmann, Josephine D Salvamoser, Maruja L Rettenbeck, Takafumi Komori, Heidrun Potschka
OBJECTIVE: Anticonvulsive monotherapy fails to be effective in one third of patients with epilepsy resulting in the need for polytherapy regimens. However, with the still limited knowledge, drug choices for polytherapy remain empirical. Here we report experimental data from a chronic epilepsy model for the combination of perampanel and zonisamide, which can render guidance for clinical studies and individual drug choices. METHODS: The anticonvulsant effects of the combination of perampanel and zonisamide were evaluated in a rat amygdala kindling model...
April 2016: Epilepsia
https://www.readbyqxmd.com/read/26845536/resveratrol-induces-intracellular-ca-2-rise-via-t-type-ca-2-channels-in-a-mesothelioma-cell-line
#17
Carla Marchetti, Stefania Ribulla, Valeria Magnelli, Mauro Patrone, Bruno Burlando
AIMS: Intracellular calcium (Ca(2+)) is known to play an important role in cancer development and growth. Resveratrol (Res) is a stilbene polyphenol occurring in several plant species and known for various possible beneficial effects, including its ability to inhibit proliferation and to induce apoptosis in cancer cells. This study was designed to determine whether Res affects Ca(2+) signaling in cancer cells. MAIN METHODS: We used the REN human mesothelioma cell line, as an in vitro cancer cell model, and the non-malignant human mesothelial MeT5A cell line, as normal cell model...
March 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/26797466/even-a-pooled-analysis-does-not-resolve-the-debate-of-electrophysiology-testing-in-brugada-syndrome
#18
EDITORIAL
Emile G Daoud
No abstract text is available yet for this article.
February 16, 2016: Circulation
https://www.readbyqxmd.com/read/26661765/two-distinct-oscillatory-states-determined-by-the-nmda-receptor-in-rat-inferior-olive
#19
Dimitris G Placantonakis, John P Welsh
1 The effects of N-methyl-d-aspartate (NMDA) receptor activation and blockade on subthreshold membrane potential oscillations of inferior olivary neurones were studied in brainstem slices from 12- to 21-day-old rats. 2 Dizocilpine (MK-801), a non-competitive NMDA antagonist, at 1-45 μm abolished spontaneous subthreshold oscillations, without affecting membrane potential, input resistance, or the low-threshold calcium current, IT . Ketamine (100 μm), a non-competitive NMDA antagonist, and L-689,560 (20 μm), an antagonist at the glycine site of the NMDA receptor, also abolished the oscillations, while the competitive non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20-50 μm) had no effect...
July 2001: Journal of Physiology
https://www.readbyqxmd.com/read/26627919/contribution-of-postsynaptic-t-type-calcium-channels-to-parallel-fibre-purkinje-cell-synaptic-responses
#20
Romain Ly, Guy Bouvier, German Szapiro, Haydn M Prosser, Andrew D Randall, Masanobu Kano, Kenji Sakimura, Philippe Isope, Boris Barbour, Anne Feltz
KEY POINTS: At the parallel fibre-Purkinje cell glutamatergic synapse, little or no Ca(2+) entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid postsynaptic Ca(2+) signalling mechanism, making it essential to understand how they contribute to the synaptic signalling. Using a selective T-type calcium channel antagonist, we describe a T-type component of the EPSC that is activated by the AMPA receptor-mediated depolarization of the spine and thus will contribute to the local calcium dynamics...
February 15, 2016: Journal of Physiology
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