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https://www.readbyqxmd.com/read/29675583/do-alcohol-related-ampa-type-glutamate-receptor-adaptations-promote-intake
#1
F Woodward Hopf, Regina A Mangieri
Ionotropic glutamate receptors (AMPA, NMDA, and kainate receptors) play a central role in excitatory glutamatergic signaling throughout the brain. As a result, functional changes, especially long-lasting forms of plasticity, have the potential to profoundly alter neuronal function and the expression of adaptive and pathological behaviors. Thus, alcohol-related adaptations in ionotropic glutamate receptors are of great interest, since they could promote excessive alcohol consumption, even after long-term abstinence...
April 20, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29665428/enhanced-sampling-of-the-glutamate-receptor-ligand-binding-domain
#2
REVIEW
Albert Y Lau
The majority of excitatory synaptic transmission in the central nervous system is mediated by ionotropic glutamate receptors (iGluRs). These membrane-bound protein assemblies consist of modular domains that can be genetically isolated and expressed, which has resulted in a plethora of crystal structures of individual domains in different conformations bound to different ligands. These structures have presented opportunities for molecular dynamics (MD) simulation studies. To examine the free energies that govern molecular behavior, simulation strategies and algorithms have been developed, collectively called enhanced sampling methods This review focuses on the use of enhanced sampling MD simulations of isolated iGluR ligand-binding domains to characterize thermodynamic properties important to receptor function...
April 14, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29623852/potential-future-of-new-glutamate-agonists-and-antagonists-development
#3
Dariusz Matosiuk
Receptors of glutamic acid are known for over 30 years for their action and for about 20 years for their structure. Presence of at least three classes of ionotropic receptors was confirmed at the beginning of 80' [1]. Recognition of the sequence [2,3] and first cloning were done at the beginning of 90' [4-6]. In 1994 ligand binding site was recognized at the junction of two subunits S1-S2 in the ligand binding domain [7]. Since then many subtypes of ionotropic and metabotropic glutamate receptors were recognized, together with their localization and functions...
April 4, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29618286/neuronal-activity-dependent-control-of-postnatal-neurogenesis-and-gliogenesis
#4
Ragnihldur T Káradóttir, Chay T Kuo
The addition of new neurons and oligodendroglia in the postnatal and adult mammalian brain presents distinct forms of gray and white matter plasticity. Substantial effort has been devoted to understanding the cellular and molecular mechanisms controlling postnatal neurogenesis and gliogenesis, revealing important parallels to principles governing the embryonic stages. While during central nervous system development, scripted temporal and spatial patterns of neural and glial progenitor proliferation and differentiation are necessary to create the nervous system architecture, it remains unclear what driving forces maintain and sustain postnatal neural stem cell (NSC) and oligodendrocyte progenitor cell (OPC) production of new neurons and glia...
April 4, 2018: Annual Review of Neuroscience
https://www.readbyqxmd.com/read/29607693/sublingual-spray-drug-delivery-of-ketorolac-loaded-chitosan-nanoparticles
#5
Sarah Baltzley, Azzam A Malkawi, Motasem Alsmadi, Abeer M Al-Ghananeem
INTRODUCTION: The aim of this study was to investigate Ketorolac (KT) systemic absolute bioavailability after sublingual (SL) administration in vivo to conscious rabbits. Furthermore, the study investigated the potential use of chitosan nanoparticles as a delivery system to enhance the systemic bioavailability of KT following sublingual administration. METHODS: Ketorolac-loaded chitosan nanoparticles were prepared through ionotropic gelation of chitosan with tripolyphosphate anions...
April 2, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29607422/ion-permeation-in-ionotropic-glutamate-receptors-still-dynamic-after-all-these-years
#6
Lonnie P Wollmuth
Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the vast majority of fast synaptic transmission in the nervous system. When the iGluR ion channel is in the open or conducting conformation, it is non-selective for monovalent cations, driving membrane excitation. Often the channel is also permeable to Ca2+ . This process of Ca2+ permeation and its physiological and pathological consequences depend strongly on the specific iGluR subtype as well as the specific subunits in the oligomeric complex...
April 2018: Current Opinion in Physiology
https://www.readbyqxmd.com/read/29605484/amn082-a-metabotropic-glutamate-receptor-type-7-allosteric-agonist-in-the-nac-facilitates-extinction-and-inhibits-the-reinstatement-of-morphine-induced-conditioned-place-preference-in-male-rats
#7
Mahsaneh Vatankhah, Abdolrahman Sarihi, Alireza Komaki, Siamak Shahidi, Abbas Haghparast
Nucleus accumbens (NAc) plays plays a primary role in opioid reward. The actions of glutamate (which is the most extensive excitatory neurotransmitter in the mammalian central nervous system) are mediated through the activation of the ionotropic and metabotropic glutamate receptors (mGluRs). Previous studies have shown the extensive distributions of the different types of mGluRs, including mGluR7, in regions that are involved in opioid reward, such as NAc. In this study, CPP was used to investigate the effect of mGluR7 on the extinction period, and the reinstatement of morphine...
March 29, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29601975/application-of-a-simple-desolvation-method-to-increase-the-formation-yield-physical-stability-and-hydrophobic-drug-encapsulation-capacity-of-chitosan-based-nanoparticles
#8
Liqun Jiang, Huajian Duan, Xiangxiang Ji, Tingyu Wang, Yun Wang, Jingying Qiu
As one of the classical nano drug carriers, chitosan-based nanoparticles (CsNps) are getting increasing attentions for their non-toxicity, biocompatibility and biodegradability. The ionotropic gelation is the most favorable method for CsNps preparation, while it's beset by some issues, i.e. low particle formation yield, poor physical stability and low hydrophobic drug loading capacity. To solve these problems, a simple desolvation method was attempted in this study for CsNps preparation. Using this method, an increased formation yield of CsNps (about 100%) could be obtained, and after diluting the particles by various buffers (PBS7...
March 27, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29601577/an-open-source-tool-for-automatic-spatiotemporal-assessment-of-calcium-transients-and-local-signal-close-to-noise-activity-in-calcium-imaging-data
#9
Juan Prada, Manju Sasi, Corinna Martin, Sibylle Jablonka, Thomas Dandekar, Robert Blum
Local and spontaneous calcium signals play important roles in neurons and neuronal networks. Spontaneous or cell-autonomous calcium signals may be difficult to assess because they appear in an unpredictable spatiotemporal pattern and in very small neuronal loci of axons or dendrites. We developed an open source bioinformatics tool for an unbiased assessment of calcium signals in x,y-t imaging series. The tool bases its algorithm on a continuous wavelet transform-guided peak detection to identify calcium signal candidates...
March 30, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29597332/makaluvamine-g-from-the-marine-sponge-zyzzia-fuliginosa-inhibits-muscle-nachr-by-binding-at-the-orthosteric-and-allosteric-sites
#10
Denis S Kudryavtsev, Ekaterina N Spirova, Irina V Shelukhina, Lina V Son, Yana V Makarova, Natalia K Utkina, Igor E Kasheverov, Victor I Tsetlin
Diverse ligands of the muscle nicotinic acetylcholine receptor (nAChR) are used as muscle relaxants during surgery. Although a plethora of such molecules exists in the market, there is still a need for new drugs with rapid on/off-set, increased selectivity, and so forth. We found that pyrroloiminoquinone alkaloid Makaluvamine G (MG) inhibits several subtypes of nicotinic receptors and ionotropic γ-aminobutiric acid receptors, showing a higher affinity and moderate selectivity toward muscle nAChR. The action of MG on the latter was studied by a combination of electrophysiology, radioligand assay, fluorescent microscopy, and computer modeling...
March 28, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29593052/long-term-depression-is-independent-of-glun2-subunit-composition
#11
Jonathan M Wong, John A Gray
NMDA receptors (NMDARs) mediate both long-term potentiation (LTP) and long-term depression (LTD) and understanding how a single receptor can initiate both phenomena remains a major question in neuroscience. A prominent hypothesis implicates the NMDAR subunit composition, specifically GluN2A and GluN2B, in dictating the rules of synaptic plasticity. However, studies testing this hypothesis have yielded inconsistent and often contradictory results, especially for LTD. These inconsistent results may be due to challenges in the interpretation of subunit-selective pharmacology and in dissecting out the contributions of differential channel properties versus the interacting proteins unique to GluN2A or GluN2B...
March 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29588343/ionotropic-and-metabotropic-mechanisms-of-allosteric-modulation-of-%C3%AE-7-nicotinic-receptor-intracellular-calcium
#12
Justin R King, Aman Ullah, Ellen Bak, Saleet Jafri, Nadine Kabbani
The pharmacological targeting of the α7 nicotinic acetylcholine receptor (α7) is a promising strategy in the development of new drugs for neurological diseases Because α7 receptors regulate cellular calcium, we investigated how the prototypical type II positive allosteric modulator PNU120596 affects α7 mediated calcium signaling. Live imaging experiments show that PNU120596 augments ryanodine receptor driven calcium-induced calcium release (CICR), IP3 induced calcium release (IICR), and PLC activation by the α7 receptor...
March 27, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29588040/hcn-and-k-2p-channels-in-anesthetic-mechanisms-research
#13
Paul M Riegelhaupt, Gareth R Tibbs, Peter A Goldstein
The ability of a diverse group of agents to produce general anesthesia has long been an area of intense speculation and investigation. Over the past century, we have seen a paradigm shift from proposing that the anesthetized state arises from nonspecific interaction of anesthetics with the lipid membrane to the recognition that the function of distinct, and identifiable, membrane-embedded proteins is dramatically altered in the presence of intravenous and inhaled agents. Among proteinaceous targets, metabotropic and ionotropic receptors garnered much of the attention over the last 30 years, and it is only relatively recently that voltage-gated ion channels have clearly and rigorously been shown to be important molecular targets...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29582401/trpv4-a-sensor-for-homeostasis-and-pathological-events-in-the-cns
#14
REVIEW
Hemant Kumar, Soo-Hong Lee, Kyoung-Tae Kim, Xiang Zeng, Inbo Han
Transient receptor potential vanilloid type 4 (TRPV4) was originally described as a calcium-permeable nonselective cation channel. TRPV4 is now recognized as a polymodal ionotropic receptor: it is a broadly expressed, nonselective cation channel (permeable to calcium, potassium, magnesium, and sodium) that plays an important role in a multitude of physiological processes. TRPV4 is involved in maintaining homeostasis, serves as an osmosensor and thermosensor, can be activated directly by endogenous or exogenous chemical stimuli, and can be activated or sensitized indirectly via intracellular signaling pathways...
March 26, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29572431/a-gain-of-function-mutation-in-the-%C3%AE-9-nicotinic-acetylcholine-receptor-alters-medial-olivocochlear-efferent-short-term-synaptic-plasticity
#15
Carolina Wedemeyer, Lucas G Vattino, Marcelo J Moglie, Jimena Ballestero, Stéphane F Maison, Mariano N Di Guilmi, Julian Taranda, M Charles Liberman, Paul A Fuchs, Eleonora Katz, Ana Belén Elgoyhen
Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher processing centers. Efferent activation inhibits OHC active amplification within the mammalian cochlea, through the activation of a calcium permeable α9α10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels...
March 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29566459/enormous-expansion-of-the-chemosensory-gene-repertoire-in-the-omnivorous-german-cockroach-blattella-germanica
#16
Hugh M Robertson, Rachel L Baits, Kimberly K O Walden, Ayako Wada-Katsumata, Coby Schal
The acquisition of genome sequences from a wide range of insects and other arthropods has revealed a broad positive correlation between the complexity of their chemical ecology and the size of their chemosensory gene repertoire. The German cockroach Blattella germanica is an extreme omnivore and has the largest chemosensory gene repertoire known for an arthropod, exceeding even the highly polyphagous spider mite Tetranychus urticae. While the Odorant Receptor family is not particularly large, with 123 genes potentially encoding 134 receptors (105 intact), the Gustatory Receptor family is greatly expanded to 431 genes potentially encoding 545 receptors (483 intact), the largest known for insects and second only to the spider mite...
March 22, 2018: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/29564678/weighted-burden-analysis-of-exome-sequenced-case-control-sample-implicates-synaptic-genes-in-schizophrenia-aetiology
#17
David Curtis, Leda Coelewij, Shou-Hwa Liu, Jack Humphrey, Richard Mott
A previous study of exome-sequenced schizophrenia cases and controls reported an excess of singleton, gene-disruptive variants among cases, concentrated in particular gene sets. The dataset included a number of subjects with a substantial Finnish contribution to ancestry. We have reanalysed the same dataset after removal of these subjects and we have also included non-singleton variants of all types using a weighted burden test which assigns higher weights to variants predicted to have a greater effect on protein function...
March 21, 2018: Behavior Genetics
https://www.readbyqxmd.com/read/29563872/the-metabotropic-purinergic-p2y-receptor-family-as-novel-drug-target-in-epilepsy
#18
REVIEW
Mariana Alves, Edward Beamer, Tobias Engel
Epilepsy encompasses a heterogeneous group of neurological syndromes which are characterized by recurrent seizures affecting over 60 million people worldwide. Current anti-epileptic drugs (AEDs) are mainly designed to target ion channels and/or GABA or glutamate receptors. Despite recent advances in drug development, however, pharmacoresistance in epilepsy remains as high as 30%, suggesting the need for the development of new AEDs with a non-classical mechanism of action. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29559921/nitric-oxide-orchestrates-a-power-law-modulation-of-sympathetic-firing-behaviors-in-neonatal-rat-spinal-cords
#19
Chun-Kuei Su, Yi-Yin Chen, Chiu-Ming Ho
Nitric oxide (NO) is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using in vitro preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29550814/effects-of-kudingcha-nanoparticles-in-hyperlipidaemic-rats-induced-by-a-high-fat-diet
#20
Hongliang Zhang, Xiaoqin Zou, Qiuyan Huang, Xiaobin Zhong, Zhenguang Huang
BACKGROUND/AIMS: The herbal medicine Kudingcha has a bitter taste and low bioavailability for lipid reduction. To improve the bioavailability and ameliorate the compliance, we prepared Kudingcha nanoparticles and investigated their effect in hyperlipidaemic rats. In addition, the safety and lipid-lowering mechanism of the Kudingcha nanoparticles were examined. METHODS: Kudingcha nanoparticles were prepared by ionotropic gelation and spray-drying. Seventy rats were randomly assigned into eight groups: a normal fat diet group (NF), a high-fat group (HF), a spontaneous recovery group (SR), a Kudingcha group (KDC), a blank nanoparticle group (B-N), and a Kudingcha nanoparticle groups (low, medium and high doses)...
March 10, 2018: Cellular Physiology and Biochemistry
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