Imperial College London

DrRobertDickinson

Faculty of MedicineDepartment of Surgery & Cancer

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 7633r.dickinson

 
 
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Location

 

Biophysics Group, Room 403Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

60 results found

Armstrong SP, Banks P, McKitrick T, Geldart C, Edge C, Babla R, Simillis C, Franks NP, Dickinson Ret al., 2012, Mutations in the NMDA receptor glycine site prevent competitive inhibition by xenon without affecting inhibition by sevoflurane or isoflurane, Society for Neuroscsince Meeting, New Orleans

Conference paper

Armstrong SP, Banks PJ, McKitrick TJW, Geldart CHG, Edge CJE, Babla R, Simillis C, Franks NP, Dickinson Ret al., 2012, Identification of two mutations (F758W & F758Y) in the NMDA receptor glycine-binding site that prevent competitive inhibition by xenon without affecting glycine binding, Anesthesiology, Vol: 117, Pages: 38-47, ISSN: 1528-1175

BACKGROUND: Xenon is a general anesthetic with neuroprotective properties. Xenon inhibition at the glycine-binding site of the N-Methyl-D-aspartate (NMDA) receptor mediates xenon neuroprotection against ischemic injury in vitro. Here we identify specific amino acids important for xenon binding to the NMDA receptor, with the aim of finding silent mutations that eliminate xenon binding but leave normal receptor function intact.METHODS:Site-directed mutagenesis was used to mutate specific amino-acids in the GluN1 subunit of rat NMDA receptors. Mutant GluN1/GluN2A receptors were expressed in HEK 293 cells and were assessed functionally using patch-clamp electrophysiology. The responses of the mutant receptors to glycine and anesthetics were determined.RESULTS:Mutation of phenylalanine 758 to an aromatic tryptophan or tyrosine left glycine affinity unchanged, but eliminated xenon binding without affecting the binding of sevoflurane or isoflurane.CONCLUSIONS:These findings confirm xenon binds to the glycine site of the GluN1 subunit of the NMDA receptor and indicate that interactions between xenon and the aromatic ring of the phenylalanine 758 residue are important for xenon binding. Our most important finding is that we have identified two mutations, F758W and F758Y, that eliminate xenon binding to the NMDA receptor glycine site without changing the glycine affinity of the receptor or the binding of volatile anesthetics. The identification of these selective mutations will allow knock-in animals to be used to dissect the mechanism(s) of xenon's neuroprotective and anesthetic properties in vivo.

Journal article

Geldart CH, Banks P, Mckitrick TJW, Franks NP, Dickinson Ret al., 2011, A specific amino acid in the glycine-binding site of the N-methyl-D-aspartate receptor is involved in xenon inhibition of the N-methyl-D-aspartate receptor, British Journal of Anaesthesia, Vol: 106

Journal article

Banks P, Franks NP, 2011, The NMDA receptor glycine site mediates xenon neuroprotection against hypoxic/ischemic injury, 25th International Symposium on Cerebral Blood Flow, Metabolism & Function, Barcelona

Conference paper

Dickinson R, Franks NP, 2010, Bench-to-bedside review: molecular pharmacology and clinical use of inert gases in anesthesia and neuroprotection, Critical Care, Vol: 14, ISSN: 1364-8535

In the past decade there has been a resurgence of interest in the clinical use of inert gases. In the present paper we review the use of inert gases as anesthetics and neuroprotectants, with particular attention to the clinical use of xenon. We discuss recent advances in understanding the molecular pharmacology of xenon and we highlight specific pharmacological targets that may mediate its actions as an anesthetic and neuroprotectant. We summarize recent in vitro and in vivo studies on the actions of helium and the other inert gases, and discuss their potential to be used as neuroprotective agents.

Journal article

Banks P, Franks NP, Dickinson R, 2010, Xenon neuroprotection against hypoxia-ischaemia is mediated by the N-methyl-D-aspartate receptor glycine site, Meeting of the Anaesthetic-Research-Society, Publisher: OXFORD UNIV PRESS, Pages: 526-526, ISSN: 0007-0912

Conference paper

Banks P, Franks NP, Dickinson R, 2010, Competitive Inhibition at the Glycine Site of the N-Methyl-D-Aspartate Receptor Mediates Xenon Neuroprotection against Hypoxia-Ischemia, ANESTHESIOLOGY, Vol: 112, Pages: 614-622, ISSN: 0003-3022

Journal article

Banks P, Franks NP, Dickinson R, 2010, Xenon neuroprotection against hypoxic/ischemic injury is mediated by inhibition of the NMDA-receptor at the glycine site, 8th International Conference on Anaesthetic Mechanisms

Conference paper

Banks P, Franks NP, Dickinson R, 2010, Xenon neuroprotection against hypoxia-ischemia is mediated by the N-methyl-D-aspartate receptor glycine site, British Journal of Anaesthesia, Vol: 104

Journal article

Geldart CH, Banks P, McKitrick TJW, Franks NP, Dickinson Ret al., 2010, A specific amino acid in the glycine-binding site of the N-methyl-D-aspartate receptor is involved in xenon inhibition of the N-methyl-D-aspartate receptor, Anaesthetic Research Society Meeting

Conference paper

Dickinson R, Franks NP, 2010, Molecular Pharmacology of Inert Gases as Anaesthetics and Neuroprotectants, Critical Care, Vol: 14

Journal article

Banks P, Franks NP, Dickinson R, 2009, Xenon neuroprotection against hypoxia-ischemia is mediated by the NMDA-receptor glycine site, Anesthetic Research Society

Conference paper

Andres-Enguix I, Caley A, Yustos R, Schumacher M A, Spanu P D, Dickinson R, Maze M, Franks N Pet al., 2007, Determinants of the anesthetic sensitivity of two-pore domain acid-sensitive potassium channels: molecular cloning of an anesthetic-activated potassium channelfrom Lymnaea stagnalis, Journal of Biological Chemistry, Vol: 282, Pages: 20977-20990, ISSN: 0021-9258

Journal article

Dickinson R, Peterson B, Banks P, Simillis C, Martin JC, Valenzuela CA, Maze M, Franks NPet al., 2007, Competitive Inhibition at the Glycine Site of the NMDA Receptor by the Anesthetics Xenon and Isoflurane: Evidence from Molecular Modeling and Electrophysiology, Anesthesiology, Vol: 107, Pages: 756-767

Journal article

White IL, Franks NP, Dickinson R, 2005, Effects of isoflurane and xenon on Ba2+-currents mediated by N-type calcium channels, BRITISH JOURNAL OF ANAESTHESIA, Vol: 94, Pages: 784-790, ISSN: 0007-0912

Journal article

Dickinson R, Awaiz S, Whittington MA, Lieb WR, Franks NPet al., 2003, The effects of general anaesthetics on carbachol-evoked gamma oscillations in the rat hippocampus in vitro, NEUROPHARMACOLOGY, Vol: 44, Pages: 864-872, ISSN: 0028-3908

Journal article

Dickinson R, de Sousa SLM, Lieb WR, Franks NPet al., 2002, Selective synaptic actions of thiopental and its enantiomers, ANESTHESIOLOGY, Vol: 96, Pages: 884-892, ISSN: 0003-3022

Journal article

Dickinson R, De Sousa SLM, Lieb WR, Franks NPet al., 2001, The effects of xenon on NMDA and GABAA receptors, Pages: 34-36, ISSN: 0941-4223

Conference paper

Dickinson R, White I, Lieb WR, Franks NPet al., 2000, Stereoselective loss of righting reflex in rats by isoflurane, ANESTHESIOLOGY, Vol: 93, Pages: 837-843, ISSN: 0003-3022

Journal article

de Sousa SLM, Dickinson R, Lieb WR, Franks NPet al., 2000, Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon, ANESTHESIOLOGY, Vol: 92, Pages: 1055-1066, ISSN: 0003-3022

Journal article

Franks NP, Dickinson R, de Sousa SL, Hall AC, Lieb WRet al., 1998, How does xenon produce anaesthesia?, Nature, Vol: 396

Journal article

Dickinson R, Lieb WR, Franks NP, 1996, The effects of temperature on the interactions between volatile general anaesthetics and a neuronal nicotinic acetylcholine receptor (vol 116, pg 2949, 1995), BRITISH JOURNAL OF PHARMACOLOGY, Vol: 117, Pages: 1369-1369, ISSN: 0007-1188

Journal article

Dickinson R, Lieb WR, Franks NP, 1996, Erratum: The effects of temperature on the interactions between volatile general anaesthetics and a neuronal nicotinic acetylcholine receptor (British Journal of Pharmacology (1995) 116 (2949-2956)), British Journal of Pharmacology, Vol: 117, ISSN: 0007-1188

Journal article

DICKINSON R, LIEB WR, FRANKS NP, 1995, THE EFFECTS OF TEMPERATURE ON THE INTERACTIONS BETWEEN VOLATILE GENERAL-ANESTHETICS AND A NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 116, Pages: 2949-2956, ISSN: 0007-1188

Journal article

DICKINSON R, FRANKS NP, LIEB WR, 1994, CAN THE STEREOSELECTIVE EFFECTS OF THE ANESTHETIC ISOFLURANE BE ACCOUNTED FOR BY LIPID SOLUBILITY, BIOPHYSICAL JOURNAL, Vol: 66, Pages: 2019-2023, ISSN: 0006-3495

Journal article

Dickinson R, Franks NP, Lieb WR, 1994, Erratum: (Biophysical Journal (1994) 66 (2019-2023)), Biophysical Journal, Vol: 67, ISSN: 0006-3495

Journal article

DICKINSON R, FRANKS NP, LIEB WR, 1993, THERMODYNAMICS OF ANESTHETIC PROTEIN INTERACTIONS - TEMPERATURE STUDIES ON FIREFLY LUCIFERASE, BIOPHYSICAL JOURNAL, Vol: 64, Pages: 1264-1271, ISSN: 0006-3495

Journal article

DICKINSON R, SMITH EH, FRANKS NP, LIEB WRet al., 1993, SYNTHESIS AND USE OF THE N-BROMODODECANE-1,12-DIOLS AS CONFORMATIONAL PROBES FOR GENERAL ANESTHETIC TARGET SITES, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 36, Pages: 111-118, ISSN: 0022-2623

Journal article

MCKENZIE JD, CALOW P, CLYDE J, MILES A, DICKINSON R, LIEB WR, FRANKS NPet al., 1992, EFFECTS OF TEMPERATURE ON THE ANESTHETIC POTENCY OF HALOTHANE, ENFLURANE AND ETHANOL IN DAPHNIA-MAGNA (CLADOCERA, CRUSTACEA), COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY, Vol: 101, Pages: 15-19, ISSN: 0742-8413

Journal article

CURRY S, MOSS GWJ, DICKINSON R, LIEB WR, FRANKS NPet al., 1991, PROBING THE MOLECULAR DIMENSIONS OF GENERAL ANESTHETIC TARGET SITES IN TADPOLES (XENOPUS-LAEVIS) AND MODEL SYSTEMS USING CYCLOALCOHOLS, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 102, Pages: 167-173, ISSN: 0007-1188

Journal article

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