A5025249043- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Cholinesterase and Neurodegenerative Diseases
- Neurotransmitter Receptor Influence on Behavior
- Plant-based Medicinal Research
- Marine Toxins and Detection Methods
- Insect and Pesticide Research
- Photoreceptor and optogenetics research
- Synthesis and Biological Evaluation
- Pharmacological Receptor Mechanisms and Effects
- Chemical synthesis and alkaloids
- Memory and Neural Mechanisms
- bioluminescence and chemiluminescence research
- Botulinum Toxin and Related Neurological Disorders
- Cancer, Stress, Anesthesia, and Immune Response
- Smoking Behavior and Cessation
- Stress Responses and Cortisol
- Alkaloids: synthesis and pharmacology
- Neuropeptides and Animal Physiology
- Neuroendocrine regulation and behavior
- Chemical Synthesis and Analysis
- Cellular transport and secretion
- Monoclonal and Polyclonal Antibodies Research
University of Bath
2014-2025
British Pharmacological Society
2015-2018
SRI International
2011
Menlo School
2011
University of Bristol
1997-2003
University College London
2002
University of Alberta
1994
Transnational Press London
1992
University of Maryland, Baltimore
1987-1990
University of Baltimore
1990
Reproducibility is a current concern for everyone involved in the conduct and publication of biomedical research. Recent attempts testing reproducibility, particularly reproducibility project cancer biology published elife (https://elifesciences.org/collections/9b1e83d1/reproducibility-project-cancer-biology), have exposed major difficulties repeating preclinical experimental work. It thought that some these relate to uncertainty about provenance tools, lack clarity methodology use...
Abstract: This study establishes that presynaptic nicotinic receptors modulate dopamine release in the mouse striatum. Nicotinic agonists elicit a dose‐dependent increase of [ 3 H]dopamine from synaptosomes prepared At low concentrations, this is Ca 2+ dependent, whereas at higher concentrations ‐independent, mecamylamine‐insensitive was also observed. The ‐dependent nicotine‐evoked not blocked by α‐bungarotoxin but effectively neuronal bungarotoxin as well several other receptor...
The modulation of dopamine release by presynaptic nicotinic receptors in vitro is well established, but the significance this effect vivo unclear. We have characterised nicotine, locally applied via a microdialysis probe, on from terminal regions three ascending dopaminergic pathways conscious, freely moving rats. Nicotine caused dose-dependent increase striatum, nucleus accumbens, and, to lesser extent, frontal cortex. Metabolite levels were unaltered any concentration nicotine. Prior...
α7 neuronal nicotinic acetylcholine receptors (nAChRs) constitute one of the predominant nAChR subtypes in mammalian brain. Within ventral tegmental area (VTA), nicotine application, paired with postsynaptic stimulation, contributes to a form long-term potentiation, an effect attributed presynaptic nAChRs on glutamatergic afferents (Mansvelder and McGehee, 2000). The aim this study was examine precise subcellular distribution adult rat VTA establish whether these are indeed present axon...
Methyllycaconitine, a toxin isolated from the seeds of Delphinium brownii, inhibited acetylcholine- and anatoxin-induced whole-cell currents in cultured fetal rat hippocampal neurons, at picomolar concentrations. This antagonism was specific, concentration dependent, reversible, voltage independent. Furthermore, methyllycaconitine 125I-alpha-bungarotoxin binding to adult membranes, protected against alpha-bungarotoxin-induced pseudoirreversible blockade nicotinic currents, shifted...
6-Hydroxydopamine is a neurotoxin commonly used to lesion dopaminergic pathways and generate experimental models for Parkinson disease, however, the cellular mechanism of 6-hydroxydopamine-induced neurodegeneration not well defined. In this study we have explored how 6-hydroxydopamine neurotoxicity initiated. We also investigated downstream signaling activated in response 6-hydroxydopamine, using neuronal-like, catecholaminergic cell line (PC12 cells) as an vitro model system. shown that...
The ability of methyllycaconitine (MLA) to inhibit the binding [ 125 I]α‐bungarotoxin rat brain membranes, frog and human muscle extracts cell line TE671 has been measured. MLA showed a markedly higher affinity for site ( K i 1.4 × 10 −9 M) than receptors ; −5 ‐10 −6 M). Structure modelling techniques were used fit structure nicotinic pharmacophore model. is first low molecular weight ligand be shown discriminate between their α‐bungarotoxinbinding counterpart in brain, as such may useful...
Nicotinic agonists elicit the release of dopamine from striatal synaptosomes by acting on presynaptic nicotinic acetylcholine receptors (nAChRs) nerve terminals. Both α3β2* and α4β2 nAChR subtypes (but not α7* nAChRs) have been implicated. Here, we compared nAChR-evoked [<sup>3</sup>H]dopamine rat synaptosome slice preparations using agonist anatoxin-a. In more integral preparation, concentration-response curve for anatoxin-a-evoked was best fitted to a two-site model, giving EC<sub>50</sub>...
Abstract: Using a sensitive perfusion system we have studied the nicotine‐induced release of [ 3 H]dopamine ([ H]DA) from striatal synaptosomes. Nicotine‐evoked was concentration dependent with an EC 50 3.8 μ M . The response to 1 nicotine comparable that 16 m K + 10 veratridine evoked larger response. All three samuli were Ca 2+ but only blocked by tetrodotoxin. Repetitive stimulations (–)‐nicotine (100 μl) at 30‐min intervals resulted in similar levels H]DA release; higher concentrations...
Abstract: Presynaptic nicotinic acetylcholine receptors on striatal nerve terminals modulate the release of dopamine. We have compared effects a number agonists and antagonists perfused synaptosome preparation preloaded with [ 3 H]dopamine. (–)‐Nicotine, acetylcholine, cytisine 1,1‐dimethyl‐4‐phenylpiperazinium iodide (DMPP), at micromolar concentrations, stimulated H]dopamine from terminals. Carbamylcholine was much weaker agonist. The actions (–)‐nicotine, cytisine, DMPP were inhibited by...
Neuronal nicotinic acetylcholine receptors (nAChR) can modulate many cellular mechanisms, such as cell survival and memory processing, which are also influenced by the serine/threonine protein kinases ERK1/2. In SH-SY5Y cells hippocampal neurones, nicotine (100 microM) increased activity of This effect was Ca2+ dependent, prevented alpha7 nAChR antagonist alpha-bungarotoxin (alpha-Bgt) an inhibitor (PD98059) upstream kinase MEK. To determine intervening steps linking entry to MEK-ERK1/2...
Nicotine can enhance working memory and attention. Activation of both alpha7 beta2(*) nicotinic acetylcholine receptors (nAChRs) in the prefrontal cortex (PFC) has been implicated these processes. The ability presynaptic nAChRs to modulate neurotransmitter release, notably glutamate is postulated contribute nicotine's effects. We have examined cellular mechanisms underlying nAChR-mediated [(3)H]d-aspartate release from PFC vitro. Using nAChR-selective agonists...
Abstract Nicotinic acetylcholine receptors (nAChR) are widely distributed in the central nervous system, where they exert a modulatory influence on synaptic transmission. For striatum, pharmacological evidence supports presence of presynaptic α3β2* and α4β2* nAChR that modulate dopamine release from nigrostriatal terminals. The objective this study was to examine precise subcellular distribution β2 subunit these neurones its localisation at sites. Double immunolabelling with tyrosine...