A5032225728- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Ion channel regulation and function
- Ion Channels and Receptors
- Amino Acid Enzymes and Metabolism
- Nicotinic Acetylcholine Receptors Study
- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Peroxisome Proliferator-Activated Receptors
- Memory and Neural Mechanisms
- Stress Responses and Cortisol
- Drug Transport and Resistance Mechanisms
- ATP Synthase and ATPases Research
- Schizophrenia research and treatment
- Cancer, Stress, Anesthesia, and Immune Response
- S100 Proteins and Annexins
- Neurotransmitter Receptor Influence on Behavior
- Nitric Oxide and Endothelin Effects
- Neuroendocrine regulation and behavior
- Animal testing and alternatives
- Computational Drug Discovery Methods
- Neurobiology and Insect Physiology Research
GlaxoSmithKline (United Kingdom)
2008-2018
GlaxoSmithKline (United States)
2014
GlaxoSmithKline (Italy)
2014
GlaxoSmithKline (China)
2011-2012
Merck (United Kingdom)
2008
University of London
2000-2007
MSD (UK) Limited (United Kingdom)
2003-2007
Merck & Co., Inc., Rahway, NJ, USA (United States)
2005
In-Q-Tel
2005
Ninewells Hospital
2003
The specific mechanisms underlying general anesthesia are primarily unknown. intravenous anesthetic etomidate acts by potentiating GABA A receptors, with selectivity for β2 and β3 subunit-containing receptors determined a single asparagine residue. We generated genetically modified mouse containing an etomidate-insensitive subunit (β2 N265S) to determine the role of subunits in etomidate-induced anesthesia. Loss pedal withdrawal reflex burst suppression electroencephalogram were still...
The NADPH oxidase (NOX) family of enzymes catalyzes the formation reactive oxygen species (ROS). NOX not only have a key role in variety physiological processes but also contribute to oxidative stress certain disease states. To date, while numerous small molecule inhibitors been reported (in particular for NOX2), none demonstrated inhibitory activity vivo. As such, there is need identification improved enable further evaluation biological functions vivo as well therapeutic potential...
In the mammalian central nervous system, transporter-mediated reuptake may be critical for terminating neurotransmitter action of D-serine at strychnine insensitive glycine site NMDA receptor. The Na(+) independent amino acid transporter alanine-serine-cysteine 1 (Asc-1) has been proposed to account synaptosomal d-serine uptake by virtue its high affinity and widespread neuronal expression throughout brain. Here, we sought validate contribution Asc-1 in mouse brain synaptosomes using gene...
Coassociation of the vanilloid transient receptor potential (Trp) ion channels, TrpV1 and TrpV2, was investigated by immunoprecipitation immunofluorescence in transfected mammalian cell lines, rat dorsal root ganglia spinal cord. TrpV1/TrpV2 heteromeric complexes were coimmunoprecipitated from human embryonic kidney cells F-11 ganglion hybridoma following their coexpression. Immunofluorescent labelling revealed colocalization TrpV2 at surface. Immunoprecipitation lysates identified a minor...
Small molecule phosphodiesterase (PDE) 4 inhibitors have long been known to show therapeutic benefit in various preclinical models of psychiatric and neurologic diseases because their ability elevate cAMP cell types the central nervous system. Despite registration first PDE4 inhibitor, roflumilast, for treatment chronic obstructive pulmonary disease, potential has never fulfilled clinic due severe dose-limiting side effects such as nausea vomiting. In this study, we describe detailed...
Abstract Transient receptor potential channel proteins (TRPs) constitute a steadily growing family of ion channels with range purported functions. It has been demonstrated that TRPV2 is activated by moderate thermal stimuli and, in the rat, expressed medium to large diameter dorsal root ganglion neurons. In this study, antisera specific for human homologue were raised and characterized immunohistochemical use. Subsequently, thorough investigation was made localization cation macaque primate...
Abstract NMDA receptors are a subclass of ionotropic glutamate receptors. They trafficked and/or clustered at synapses by the post‐synaptic density (PSD)‐95 membrane associated guanylate kinase (MAGUK) family scaffolding proteins that associate with receptor NR2 subunits via their C‐terminal serine (aspartate/glutamate) valine motifs. We have carried out systematic study investigating in heterologous expression system, association four major subtypes PSD‐95 MAGUK proteins, chapsyn‐110,...
Abstract: Coexpression in human embryonic kidney (HEK) 293 cells ofthe postsynaptic density‐95 protein (PSD‐95) with NMDA receptor NR2A or NR2Bsingle subunits NR1‐1a/NR2A and NR1‐1a/NR2B subunit combinations induced anapproximately threefold increase NR2B expression. Deletionof the NR2 C‐terminal ESDV motifs resulted loss of this increasefollowing coexpression Trunc andNR1‐1a/NR2B PSD‐95. Characterisation radioligandbinding properties [ 3 H]MK‐801 to receptors orwithout PSD‐95 showed that a...
1 Mammalian transient receptor potential (TRP) channels include the nonselective cation channel TRPV1, which is activated by a range of stimuli including low pH, vanilloids and heat. Previously, selective mutagenesis experiments identified an intracellular residue (S512Y) critical to discriminating between pH vanilloid (capsaicin) gating rat TRPV1 receptor. 2 In this study, switching equivalent in human (which has some significant differences with TRPV1) also rendered relatively insensitive...
Capsaicin (vanilloid) sensitivity has long served as the functional signature of a subset nociceptive sensory neurons. Mutagenesis studies have revealed seemingly distinct regions involved in mediating ligand binding and channel activation at capsaicin site. Residue 547 (transmembrane region 4) mediates significant species differences resiniferatoxin (RTX) sensitivity, Ser<sup>512</sup> residue is critical discriminating between pH gating. In present study, pharmacological profiles variety...
Abstract Coexpression of PSD‐95 c‐Myc with NR1‐1a/NR2A NMDA receptors in human embryonic kidney (HEK) 293 cells resulted a decrease efficacy for the glycine stimulation [ 3 H]MK801 binding similar to that previously described l ‐glutamate. The inhibition constants ( K I s) ‐glutamate and determined by H]CGP 39653 H]MDL 105 519 displacement assays, respectively, were not significantly different between coexpressed ± . increased EC 50 enhancement was also found NR1‐2a/NR2A NR1‐4b/NRA thus...
Mitochondrial permeability transition pore (mPTP) formation is well documented in isolated mitochondria. However, convincing detection of mPTP whole cells remains elusive. In this study, we describe a high-throughput assay for Ca2+-activated opening platelets using HyperCyt flow cytometry. addition, demonstrate that several nucleated cells, multiple approaches, the cyclophilin D-dependent highly challenging. Results with mitochondrial-targeted Ca2+-sensing green fluorescent protein...
5-HT6 receptors are predominantly expressed in a variety of brain regions (e.g. striatum and hippocampus) associated with cognitive processing. Targeting synthetic antagonists is promising strategy for the treatment symptoms Alzheimer's disease. Preclinical microdialysis studies have demonstrated that both gold-standard AchE inhibitor, Donepezil enhance cholinergic neurotransmission1, 2; proposed mechanism action cognition-enhancing properties3, 4. also been shown to monoaminergic...
Conference Abstract| June 01 1999 COTRANSFECTION OF PSD-95 WITH CLONED NMDA RECEPTOR SUBTYPES RESULTS IN A SELECTIVE INCREASE NR2 SUBUNIT IMMUNOREACTIVITIES A. R. Rutter; Rutter 1School of Pharmacy, 29/39 Brunswick Square, London, WCIN 1AX Search for other works by this author on: This Site PubMed Google Scholar P.L. Chazot; Chazot F.A. Stephenson Biochem Soc Trans (1999) 27 (3): A115. https://doi.org/10.1042/bst027a115c Views Icon Article contents Figures & tables Video Audio Supplementary...