Research Topics
Species | P G StrangeSummaryAffiliation: University of Reading Country: UK Publications
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Publications
Use of the GTPγS ([35S]GTPγS and Eu-GTPγS) binding assay for analysis of ligand potency and efficacy at G protein-coupled receptorsPhilip 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..
Signaling mechanisms of GPCR ligandsPhilip 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....- Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effectsP 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... - Oligomers of D2 dopamine receptors: evidence from ligand bindingPhilip 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... - Mechanisms underlying agonist efficacyP 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... - Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptorsP 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... - 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 conformationJ 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... - Agonist regulation of D(2) dopamine receptor/G protein interaction. Evidence for agonist selection of G protein subtypeY Cordeaux
School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, Berkshire RG6 6AJ, United Kingdom
J Biol Chem 276:28667-75. 2001.... - Dopamine D2 receptor dimer formation: evidence from ligand bindingD 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... - Mechanisms of G protein activation via the D2 dopamine receptor: evidence for persistent receptor/G protein interaction after agonist stimulationK 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... - Agonism and inverse agonism at dopamine D2-like receptorsP 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... - Pharmacological analysis of a dopamine D(2Short):G(alphao) fusion protein expressed in Sf9 cellsLucien 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... - Mechanisms of agonist action at D2 dopamine receptorsDavid 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... - G-protein coupled receptors: conformations and statesP 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... - Assays for enhanced activity of low efficacy partial agonists at the D(2) dopamine receptorH Lin
School of Pharmacy, University of Reading, Whiteknights, Reading, Berkshire, UK
Br J Pharmacol 149:291-9. 2006..AJ-76, aripiprazole and UH-232 seem particularly sensitive to this change in assay conditions. This work provides a new method to discover these very low efficacy agonists... - Interaction of the D2short dopamine receptor with G proteins: analysis of receptor/G protein selectivitySarah 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... - Mechanisms of inverse agonist action at D2 dopamine receptorsDavid 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... - 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 transferLucien 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... - The influence of G protein subtype on agonist action at D2 dopamine receptorsSarah 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... - Analysis of second messenger pathways stimulated by different chemokines acting at the chemokine receptor CCR5K 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... - CCL3, acting via the chemokine receptor CCR5, leads to independent activation of Janus kinase 2 (JAK2) and Gi proteinsAnja 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... - Mechanisms of ligand binding and efficacy at the human D2(short) dopamine receptorSarah L Payne
School of Animal and Microbial Sciences, University of Reading, UK
J Neurochem 82:1106-17. 2002.... - Mechanisms of internalization and recycling of the chemokine receptor, CCR5Anja 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... 
Co-operativity in agonist binding at the D2 dopamine receptor: evidence from agonist dissociation kineticsElodie 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...- Investigation of cooperativity in the binding of ligands to the D(2) dopamine receptorMeritxell 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... - 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 selectivityLucien 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... - Investigation of the mechanism of agonist and inverse agonist action at D2 dopamine receptorsDavid 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... - Inverse agonist properties of atypical antipsychotic drugsElizabeth 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... - Pathways for internalization and recycling of the chemokine receptor CCR5Anja 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... - Pharmacological characterization of the chemokine receptor, CCR5Anja 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... - Mechanisms of inverse agonism at G-protein-coupled receptorsPhilip 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... - Formation of oligomers by G protein-coupled receptorsLucien 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... - Allosteric effects of antagonists on signalling by the chemokine receptor CCR5Ben 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... - Analysis of molecular determinants of affinity and relative efficacy of a series of R- and S-2-(dipropylamino)tetralins at the 5-HT1A serotonin receptorJ 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... - Diverse signalling by different chemokines through the chemokine receptor CCR5Anja 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... - Antipsychotic drug action: antagonism, inverse agonism or partial agonismPhilip 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... - Agonist-dependent internalization of D2 receptors: Imaging quantification by confocal microscopyJulian L Goggi
MRC Clinical Science Centre, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, London, United Kingdom
Synapse 61:231-41. 2007.... - Domain swapping in the human histamine H1 receptorRemko 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....