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Research Article

Agonist stimulation at human μ opioid receptors in a [35S]GTPγS incorporation assay: observation of “bell-shaped” concentration–response relationships under conditions of strong receptor G protein coupling

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Pages 158-166 | Received 10 Mar 2015, Accepted 23 Jun 2015, Published online: 15 Oct 2015

References

  • Lagerström MC, Schiöth HB. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat Rev Drug Discov 2008;7:339–57
  • Offermanns S. G-proteins as transducers in transmembrane signalling. Prog Biophys Mol Biol 2003;83:101–30
  • Jacoby E, Bouhelal R, Gerspacher M, Seuwen K. The 7 TM G-protein-coupled receptor target family. ChemMedChem 2006;1:761–82
  • Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov 2002;1:727–30
  • Overington JP, Al Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov 2006;5:993–6
  • Siehler S. Cell-based assays in GPCR drug discovery. Biotechnol J 2008;3:471–83
  • Zhang R, Xie X. Tools for GPCR drug discovery. Acta Pharmacol Sin 2012;33:372–84
  • Kenakin T. Inverse, protean, and ligand-selective agonism: matters of receptor conformation. FASEB J 2001;15:598–611
  • Christopoulos A, El Fakahany EE. Qualitative and quantitative assessment of relative agonist efficacy. Biochem Pharmacol 1999;58:735–48
  • Bindslev N. A homotropic two-state model and auto-antagonism. BMC Pharmacol 2004;4:11
  • Owen SC, Doak AK, Ganesh AN, et al. Colloidal drug formulations can explain “bell-shaped” concentration–response curves. ACS Chem Biol 2014;9:777–84
  • Rovati GE, Nicosia S. Lower efficacy: interaction with an inhibitory receptor or partial agonism? Trends Pharmacol Sci 1994;15:140–4
  • Newman-Tancredi A, Cussac D, Marini L, Millan MJ. Antibody capture assay reveals bell-shaped concentration–response isotherms for h5-HT(1A) receptor-mediated Galpha(i3) activation: conformational selection by high-efficacy agonists, and relationship to trafficking of receptor signaling. Mol Pharmacol 2002;62:590–601
  • Heusler P, Bruins SL, Tourette A, et al. The clozapine metabolite N-desmethylclozapine displays variable activity in diverse functional assays at human dopamine D(2) and serotonin 5-HT(1)A receptors. Eur J Pharmacol 2011;669:51–8
  • Bevan N, Palmer T, Drmota T, et al. Functional analysis of a human A(1) adenosine receptor/green fluorescent protein/G(i1)alpha fusion protein following stable expression in CHO cells. FEBS Lett 1999;462:61–5
  • Zhang Q, Okamura M, Guo ZD, et al. Effects of partial agonists and Mg2+ ions on the interaction of M2 muscarinic acetylcholine receptor and G protein Galpha i1 subunit in the M2-Galpha i1 fusion protein. J Biochem 2004;135:589–96
  • Colquhoun D. Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors. Br J Pharmacol 1998;125:924–47
  • Kelly E. Efficacy and ligand bias at the mu-opioid receptor. Br J Pharmacol 2013;169:1430–46
  • Pasternak GW, Pan YX. Mu opioids and their receptors: evolution of a concept. Pharmacol Rev 2013;65:1257–317
  • Harrison C, Traynor JR. The [35S]GTPgammaS binding assay: approaches and applications in pharmacology. Life Sci 2003;74:489–508
  • Strange PG. Use of the GTPgammaS ([35S]GTPgammaS and Eu-GTPgammaS) binding assay for analysis of ligand potency and efficacy at G protein-coupled receptors. Br J Pharmacol 2010;161:1238–49
  • Chen G, Way J, Armour S, et al. Use of constitutive G protein-coupled receptor activity for drug discovery. Mol Pharmacol 2000;57:125–34
  • Katritch V, Fenalti G, Abola EE, et al. Allosteric sodium in class A GPCR signaling. Trends Biochem Sci 2014;39:233–44
  • Pauwels PJ, Tardif S, Wurch T, Colpaert FC. Stimulated [35S]GTP gamma S binding by 5-HT1A receptor agonists in recombinant cell lines. Modulation of apparent efficacy by G-protein activation state. Naunyn Schmiedebergs Arch Pharmacol 1997;356:551–61
  • Livingston KE, Traynor JR. Disruption of the Na+ ion binding site as a mechanism for positive allosteric modulation of the mu-opioid receptor. Proc Natl Acad Sci USA 2014;111:18369–74
  • Selley DE, Cao CC, Liu Q, Childers SR. Effects of sodium on agonist efficacy for G-protein activation in mu-opioid receptor-transfected CHO cells and rat thalamus. Br J Pharmacol 2000;130:987–96
  • Selley DE, Sim LJ, Xiao R, et al. mu-Opioid receptor-stimulated guanosine-5′-O-(gamma-thio)-triphosphate binding in rat thalamus and cultured cell lines: signal transduction mechanisms underlying agonist efficacy. Mol Pharmacol 1997;51:87–96
  • Eason MG, Kurose H, Holt BD, et al. Simultaneous coupling of alpha 2-adrenergic receptors to two G-proteins with opposing effects. Subtype-selective coupling of alpha 2C10, alpha 2C4, and alpha 2C2 adrenergic receptors to Gi and Gs. J Biol Chem 1992;267:15795–801
  • Michal P, Lysikova M, Tucek S. Dual effects of muscarinic M(2) acetylcholine receptors on the synthesis of cyclic AMP in CHO cells: dependence on time, receptor density and receptor agonists. Br J Pharmacol 2001;132:1217–28
  • Rauly-Lestienne I, Lestienne F, Ailhaud MC, et al. Competitive interaction of 5-HT(1A) receptors with G-protein subtypes in CHO cells demonstrated by RNA interference. Cell Signal 2011;23:58–64
  • Wade F, Espagne A, Persuy MA, et al. Relationship between homo-oligomerization of a mammalian olfactory receptor and its activation state demonstrated by bioluminescence resonance energy transfer. J Biol Chem 2011;286:15252–9
  • Ferguson SS. Phosphorylation-independent attenuation of GPCR signalling. Trends Pharmacol Sci 2007;28:173–9
  • Quirk K, Roberts DJ, Strange PG. Mechanisms of G protein activation via the D2 dopamine receptor: evidence for persistent receptor/G protein interaction after agonist stimulation. Br J Pharmacol 2007;151:144–52
  • Traynor JR, Clark MJ, Remmers AE. Relationship between rate and extent of G protein activation: comparison between full and partial opioid agonists. J Pharmacol Exp Ther 2002;300:157–61
  • Wenzel-Seifert K, Seifert R. Molecular analysis of beta(2)-adrenoceptor coupling to G(s)-, G(i)-, and G(q)-proteins. Mol Pharmacol 2000;58:954–66
  • Hommers LG, Klenk C, Dees C, Bunemann M. G proteins in reverse mode: receptor-mediated GTP release inhibits G protein and effector function. J Biol Chem 2010;285:8227–33
  • Fleysher L, Oesingmann N, Brown R, et al. Noninvasive quantification of intracellular sodium in human brain using ultrahigh-field MRI. NMR Biomed 2013;26:9–19
  • Wang D, Raehal KM, Lin ET, et al. Basal signaling activity of mu opioid receptor in mouse brain: role in narcotic dependence. J Pharmacol Exp Ther 2004;308:512–20
  • Wang D, Sun X, Sadee W. Different effects of opioid antagonists on mu-, delta-, and kappa-opioid receptors with and without agonist pretreatment. J Pharmacol Exp Ther 2007;321:544–52
  • Liu JG, Prather PL. Chronic exposure to mu-opioid agonists produces constitutive activation of mu-opioid receptors in direct proportion to the efficacy of the agonist used for pretreatment. Mol Pharmacol 2001;60:53–62
  • Kelly E, Mundell SJ, Sava A, et al. The opioid receptor pharmacology of GSK1521498 compared to other ligands with differential effects on compulsive reward-related behaviours. Psychopharmacology (Berl) 2015 Jan;232(1):305–14
  • McPherson J, Rivero G, Baptist M, et al. mu-opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization. Mol Pharmacol 2010;78:756–66
  • Alt A, McFadyen IJ, Fan CD, Woods JH, Traynor JR. Stimulation of guanosine-5′-o-(3-[35S]thio)triphosphate binding in digitonin-permeabilized C6 rat glioma cells: evidence for an organized association of mu-opioid receptors and G protein. J Pharmacol Exp Ther 2001;298:116–21
  • Clark MJ, Furman CA, Gilson TD, Traynor JR. Comparison of the relative efficacy and potency of mu-opioid agonists to activate Galpha(i/o) proteins containing a pertussis toxin-insensitive mutation. J Pharmacol Exp Ther 2006;317:858–64
  • Emmerson PJ, Clark MJ, Mansour A, et al. Characterization of opioid agonist efficacy in a C6 glioma cell line expressing the mu opioid receptor. J Pharmacol Exp Ther 1996;278:1121–7
  • Zaki PA, Keith DE Jr, Brine GA, et al. Ligand-induced changes in surface mu-opioid receptor number: relationship to G protein activation? J Pharmacol Exp Ther 2000;292:1127–34
  • Emmerson PJ, McKinzie JH, Surface PL, et al. Na+ modulation, inverse agonism, and anorectic potency of 4-phenylpiperidine opioid antagonists. Eur J Pharmacol 2004;494:121–30
  • Strange PG. Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors. Br J Pharmacol 2008;153:1353–63

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