P G Strange

Summary

Affiliation: University of Reading
Country: UK

Publications

  1. pmc Use of the GTPγS ([35S]GTPγS and Eu-GTPγS) binding assay for analysis of ligand potency and efficacy at G protein-coupled receptors
    Philip G Strange
    School of Pharmacy, University of Reading, Whiteknights, Reading, UK
    Br J Pharmacol 161:1238-49. 2010
  2. ncbi request reprint Signaling mechanisms of GPCR ligands
    Philip G Strange
    School of Pharmacy, University of Reading, PO Box 228, Whiteknights, Reading, RG6 6AJ, UK
    Curr Opin Drug Discov Devel 11:196-202. 2008
  3. ncbi request reprint Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects
    P G Strange
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, United Kingdom
    Pharmacol Rev 53:119-33. 2001
  4. ncbi request reprint Oligomers of D2 dopamine receptors: evidence from ligand binding
    Philip G Strange
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK
    J Mol Neurosci 26:155-60. 2005
  5. ncbi request reprint Mechanisms underlying agonist efficacy
    P G Strange
    School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AJ, UK
    Biochem Soc Trans 35:733-6. 2007
  6. pmc Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors
    P G Strange
    School of Pharmacy, University of Reading, Reading, Berkshire, UK
    Br J Pharmacol 153:1353-63. 2008
  7. ncbi request reprint Mechanisms of inverse agonism of antipsychotic drugs at the D(2) dopamine receptor: use of a mutant D(2) dopamine receptor that adopts the activated conformation
    J Wilson
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, UK
    J Neurochem 77:493-504. 2001
  8. ncbi request reprint Agonist regulation of D(2) dopamine receptor/G protein interaction. Evidence for agonist selection of G protein subtype
    Y Cordeaux
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, Berkshire RG6 6AJ, United Kingdom
    J Biol Chem 276:28667-75. 2001
  9. ncbi request reprint Dopamine D2 receptor dimer formation: evidence from ligand binding
    D Armstrong
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, United Kingdom
    J Biol Chem 276:22621-9. 2001
  10. pmc Mechanisms of G protein activation via the D2 dopamine receptor: evidence for persistent receptor/G protein interaction after agonist stimulation
    K Quirk
    School of Pharmacy, University of Reading, Whiteknights, Reading, UK
    Br J Pharmacol 151:144-52. 2007

Collaborators

  • Sarah A Nickolls
  • H Lin
  • P J Pauwels
  • Mark Fidock
  • Raymond G Booth
  • G Milligan
  • Lucien Gazi
  • Anja Mueller
  • David J Roberts
  • Elodie Kara
  • K Quirk
  • K Leach
  • Julian L Goggi
  • Ben Haworth
  • Meritxell Vivo
  • Elizabeth Akam
  • Remko A Bakker
  • Nasir G Mahmoud
  • J Tracy Alder
  • Sarah L Payne
  • J Wilson
  • D Armstrong
  • Y Cordeaux
  • D J Roberts
  • Pat Dorr
  • Alice Egerton
  • Paul M Grasby
  • S J Charlton
  • Alessandro Sardini
  • Rob Leurs
  • Juan F Lopez-Gimenez
  • Guido Dees
  • Juan J Carrillo
  • Uli Hacksell
  • Eamonn Kelly
  • Jane A McKeating
  • Marc C Goedecke
  • Anette M Johansson
  • S G Graber
  • L A Flood
  • J A Javitch
  • D Fu

Detail Information

Publications38

  1. pmc Use of the GTPγS ([35S]GTPγS and Eu-GTPγS) binding assay for analysis of ligand potency and efficacy at G protein-coupled receptors
    Philip G Strange
    School of Pharmacy, University of Reading, Whiteknights, Reading, UK
    Br J Pharmacol 161:1238-49. 2010
    ..LINKED ARTICLES: This article is part of a themed section on Analytical Receptor Pharmacology in Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2010.161.issue-6..
  2. ncbi request reprint Signaling mechanisms of GPCR ligands
    Philip G Strange
    School of Pharmacy, University of Reading, PO Box 228, Whiteknights, Reading, RG6 6AJ, UK
    Curr Opin Drug Discov Devel 11:196-202. 2008
    ....
  3. ncbi request reprint Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects
    P G Strange
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, United Kingdom
    Pharmacol Rev 53:119-33. 2001
    ..These variants may have different properties that alter the effects of dopamine and the antipsychotic drugs. The determination of such variants in patients may help in the prediction of drug responsiveness...
  4. ncbi request reprint Oligomers of D2 dopamine receptors: evidence from ligand binding
    Philip G Strange
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK
    J Mol Neurosci 26:155-60. 2005
    ..We propose that the receptors exist in oligomers with homotropic and heterotropic negatively cooperative interactions between ligands...
  5. ncbi request reprint Mechanisms underlying agonist efficacy
    P G Strange
    School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AJ, UK
    Biochem Soc Trans 35:733-6. 2007
    ..The [(35)S]GTP[S]-binding assay therefore determines agonist efficacy on the basis of the amount of [(35)S]GTP[S] bound rather than the rate of binding...
  6. pmc Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors
    P G Strange
    School of Pharmacy, University of Reading, Reading, Berkshire, UK
    Br J Pharmacol 153:1353-63. 2008
    ..The efficacy of a ligand may, therefore, be multidimensional. It is still, however, necessary to have accurate measures of efficacy in different pathways...
  7. ncbi request reprint Mechanisms of inverse agonism of antipsychotic drugs at the D(2) dopamine receptor: use of a mutant D(2) dopamine receptor that adopts the activated conformation
    J Wilson
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, UK
    J Neurochem 77:493-504. 2001
    ..Rather the inverse agonist appears to bind to all forms of the receptor but then renders the receptor inactive...
  8. ncbi request reprint Agonist regulation of D(2) dopamine receptor/G protein interaction. Evidence for agonist selection of G protein subtype
    Y Cordeaux
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, Berkshire RG6 6AJ, United Kingdom
    J Biol Chem 276:28667-75. 2001
    ....
  9. ncbi request reprint Dopamine D2 receptor dimer formation: evidence from ligand binding
    D Armstrong
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, United Kingdom
    J Biol Chem 276:22621-9. 2001
    ..A model of the receptor has been produced that provides a good description of the experimental phenomena described here...
  10. pmc Mechanisms of G protein activation via the D2 dopamine receptor: evidence for persistent receptor/G protein interaction after agonist stimulation
    K Quirk
    School of Pharmacy, University of Reading, Whiteknights, Reading, UK
    Br J Pharmacol 151:144-52. 2007
    ..The aim of this report is to study mechanisms of G protein activation by agonists...
  11. ncbi request reprint Agonism and inverse agonism at dopamine D2-like receptors
    P G Strange
    School of Animal and Microbial Sciences, University of Reading, United Kingdom
    Clin Exp Pharmacol Physiol Suppl 26:S3-9. 1999
    ..3. The mechanisms of agonism and inverse agonism may be probed using biochemical assays and these studies are of great relevance to the understanding of drug action...
  12. ncbi request reprint Pharmacological analysis of a dopamine D(2Short):G(alphao) fusion protein expressed in Sf9 cells
    Lucien Gazi
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, RG6 6AJ, Reading, UK
    FEBS Lett 545:155-60. 2003
    ..The D(2Short):G(alphao) fusion protein is therefore a good model for characterising D(2) receptors...
  13. ncbi request reprint Mechanisms of agonist action at D2 dopamine receptors
    David J Roberts
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, United Kingdom
    Mol Pharmacol 66:1573-9. 2004
    ..At the higher [35S]GTPgammaS concentration, for full agonists, [35S]GTPgammaS binding remains the slowest step, whereas for partial agonists, another (GDP-independent) step, probably ternary complex breakdown, becomes rate-determining...
  14. ncbi request reprint G-protein coupled receptors: conformations and states
    P G Strange
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, UK
    Biochem Pharmacol 58:1081-8. 1999
    ..Receptors and G-proteins, therefore, may exist in some form of higher order array with cooperative interactions...
  15. pmc Assays for enhanced activity of low efficacy partial agonists at the D(2) dopamine receptor
    H Lin
    School of Pharmacy, University of Reading, Whiteknights, Reading, Berkshire, UK
    Br J Pharmacol 149:291-9. 2006
    ..Low efficacy partial agonists at the D2 dopamine receptor may be useful for treating schizophrenia. In this report we describe a method for assessing the efficacy of these compounds based on stimulation of [35S]GTPgammaS binding...
  16. ncbi request reprint Interaction of the D2short dopamine receptor with G proteins: analysis of receptor/G protein selectivity
    Sarah A Nickolls
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK
    Biochem Pharmacol 65:1139-50. 2003
    ..It is concluded that the higher efficiency activation of Go by the D(2S) receptor may be a function of higher affinity receptor/G protein interaction as well as a greater ability to activate the G protein...
  17. pmc Mechanisms of inverse agonist action at D2 dopamine receptors
    David J Roberts
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ
    Br J Pharmacol 145:34-42. 2005
    ..For other compounds tested, we were unable to define the mechanism...
  18. ncbi request reprint Constitutive oligomerization of human D2 dopamine receptors expressed in Spodoptera frugiperda 9 (Sf9) and in HEK293 cells. Analysis using co-immunoprecipitation and time-resolved fluorescence resonance energy transfer
    Lucien Gazi
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, UK
    Eur J Biochem 270:3928-38. 2003
    ..Human D2 dopamine receptors can therefore form constitutive oligomers in Sf9 cells and in HEK293 cells that can be detected by different approaches, and D2 oligomerization in these cells is not regulated by ligands...
  19. ncbi request reprint The influence of G protein subtype on agonist action at D2 dopamine receptors
    Sarah A Nickolls
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK
    Neuropharmacology 47:860-72. 2004
    ..These results indicate that agonists are able to stabilise different receptor conformations with different abilities to couple to G proteins...
  20. ncbi request reprint Analysis of second messenger pathways stimulated by different chemokines acting at the chemokine receptor CCR5
    K Leach
    School of Pharmacy, University of Reading, Whiteknights, PO Box 228, Reading RG6 6AJ, United Kingdom
    Biochem Pharmacol 74:881-90. 2007
    ..It is concluded that different chemokines acting at CCR5 can induce different pharmacological responses, which may account for the broad spectrum of chemokines that can act at CCR5...
  21. ncbi request reprint CCL3, acting via the chemokine receptor CCR5, leads to independent activation of Janus kinase 2 (JAK2) and Gi proteins
    Anja Mueller
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK
    FEBS Lett 570:126-32. 2004
    ..Gi protein activation was not prevented by inhibition of JAK, showing that heterotrimeric G protein activation and activation of the JAK/signal transducer and activator of transcription (STAT) pathway are independent of each other...
  22. ncbi request reprint Mechanisms of ligand binding and efficacy at the human D2(short) dopamine receptor
    Sarah L Payne
    School of Animal and Microbial Sciences, University of Reading, UK
    J Neurochem 82:1106-17. 2002
    ....
  23. ncbi request reprint Mechanisms of internalization and recycling of the chemokine receptor, CCR5
    Anja Mueller
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, UK
    Eur J Biochem 271:243-52. 2004
    ..These data indicate that CCR5 internalization and recycling are regulated by actin polymerization and activation of small G proteins in a Rho-dependent manner...
  24. doi request reprint Co-operativity in agonist binding at the D2 dopamine receptor: evidence from agonist dissociation kinetics
    Elodie Kara
    School of Pharmacy, University of Reading, Whiteknights, Reading, UK
    J Neurochem 112:1442-53. 2010
    ..Interactions with G proteins also occurs providing further modulation of [(3)H]NPA binding. Both agonists and G proteins are proposed to modulate the oligomer by switching high affinity agonist binding sites to low affinity sites...
  25. ncbi request reprint Investigation of cooperativity in the binding of ligands to the D(2) dopamine receptor
    Meritxell Vivo
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, RG6 6AJ, UK
    Mol Pharmacol 69:226-35. 2006
    ..It may, therefore, be necessary to consider more complex models for the behavior of this receptor...
  26. pmc Functional coupling of the human dopamine D2 receptor with G alpha i1, G alpha i2, G alpha i3 and G alpha o G proteins: evidence for agonist regulation of G protein selectivity
    Lucien Gazi
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, RG6 6AJ
    Br J Pharmacol 138:775-86. 2003
    ..5) We conclude that the degree of selectivity of G protein activation by the D(2L) receptor can depend on the conformation of the receptor stabilised by an agonist...
  27. ncbi request reprint Investigation of the mechanism of agonist and inverse agonist action at D2 dopamine receptors
    David J Roberts
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, RG6 6AJ, UK
    Biochem Pharmacol 67:1657-65. 2004
    ..These data do not provide support for the idea that inverse agonists act by binding preferentially to the ground state of the receptor...
  28. ncbi request reprint Inverse agonist properties of atypical antipsychotic drugs
    Elizabeth Akam
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG66AJ, UK
    Biochem Pharmacol 67:2039-45. 2004
    ..Given that all of these antipsychotic drugs are inverse agonists, it may be concluded that this sodium ion sensitivity is unrelated to mechanisms of inverse agonism...
  29. ncbi request reprint Pathways for internalization and recycling of the chemokine receptor CCR5
    Anja Mueller
    School of Animal and Microbial Sciences, University of Reading, Reading, RG6 6AJ, United Kingdom
    Blood 99:785-91. 2002
    ..Protein synthesis is not involved in receptor recovery. It seems likely that after internalization, CCR5 is directed to early endosomes and subsequently recycled to the cell surface...
  30. pmc Pharmacological characterization of the chemokine receptor, CCR5
    Anja Mueller
    School of Animal and Microbial Sciences, The University of Reading, PO Box 228, Reading RG6 6AJ
    Br J Pharmacol 135:1033-43. 2002
    ..6. It is concluded that different chemokines interacting with CCR5 mediate different patterns of cellular responses...
  31. ncbi request reprint Mechanisms of inverse agonism at G-protein-coupled receptors
    Philip G Strange
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, RG6 6AJ, Reading, UK
    Trends Pharmacol Sci 23:89-95. 2002
    ..In this article, I consider this and other mechanisms that could explain inverse agonist actions, and conclude that more than one mechanism can apply to inverse agonism at GPCRs...
  32. ncbi request reprint Formation of oligomers by G protein-coupled receptors
    Lucien Gazi
    University of Reading, School of Animal and Microbial Sciences, Reading, RG6 6AJ, UK
    Curr Opin Drug Discov Devel 5:756-63. 2002
    ..Additionally, the trafficking of GPCRs from the cell surface may be affected by oligomerization...
  33. ncbi request reprint Allosteric effects of antagonists on signalling by the chemokine receptor CCR5
    Ben Haworth
    School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AJ, UK
    Biochem Pharmacol 74:891-7. 2007
    ..When CHO-CCR5 cells were treated with either of the two compounds for prolonged periods of time (24 h) an increase (approximately 15%) in cell surface CCR5 was detected...
  34. pmc Analysis of molecular determinants of affinity and relative efficacy of a series of R- and S-2-(dipropylamino)tetralins at the 5-HT1A serotonin receptor
    J Tracy Alder
    School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, Berkshire RG6 6AJ U K
    Br J Pharmacol 138:1129-39. 2003
    ..5. Simulations of agonist binding and effect data were performed using the Ternary Complex Model in order to assess the use of K(l)/K(h) for predicting the relative efficacy of agonists...
  35. ncbi request reprint Diverse signalling by different chemokines through the chemokine receptor CCR5
    Anja Mueller
    School of Animal and Microbial Sciences, University of Reading, PO Box 228, Reading, RG6 6AJ, UK
    Biochem Pharmacol 72:739-48. 2006
    ..The use of different assay systems, therefore, provides different estimates of efficacy for some ligands at this receptor...
  36. doi request reprint Antipsychotic drug action: antagonism, inverse agonism or partial agonism
    Philip G Strange
    School of Pharmacy, PO Box 228, University of Reading, Whiteknights, Reading RG6 6AJ, UK
    Trends Pharmacol Sci 29:314-21. 2008
    ..It seems that the treatment outcome might depend on the overall level of cell stimulation, which is in turn dependent on the level of residual dopamine and the efficacy of the drug in signalling assays...
  37. ncbi request reprint Agonist-dependent internalization of D2 receptors: Imaging quantification by confocal microscopy
    Julian L Goggi
    MRC Clinical Science Centre, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, London, United Kingdom
    Synapse 61:231-41. 2007
    ....
  38. ncbi request reprint Domain swapping in the human histamine H1 receptor
    Remko A Bakker
    Leiden Amsterdam Center for Drug Research, Faculty of Sciences, Department of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081HV Amsterdam, The Netherlands
    J Pharmacol Exp Ther 311:131-8. 2004
    ....