The evasive nature of drug efficacy: implications for drug discovery

Trends in Pharmacological Sciences

Volumn 28, Issue 8, 2007, Pages 423-430

  Galandrin, Ségolène ^a   Oligny Longpré, Geneviève ^a   Bouvier, Michel ^a  

^a INSTITUTE FOR RESEARCH IN IMMUNOLOGY AND CANCER   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; PARATHYROID HORMONE RECEPTOR;

ANALYTIC METHOD; DRUG RESEARCH; PRIORITY JOURNAL; REVIEW;

ANIMALS; DRUG DESIGN; HUMANS; MODELS, BIOLOGICAL; PHARMACEUTICAL PREPARATIONS; PROTEIN BINDING; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 34447642715     PISSN: 01656147     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tips.2007.06.005     Document Type: Review

References (81)

1. Clark A.J. General Pharmacology: Heffter's Handbuch d. exp.Pharmacology (1937), Springer
2. Clark A.J. The Mode Of Action Of Drugs On Cells (1933), Edward Arnold
3. Stephenson R.P. A modification of receptor theory 1956. Br. J. Pharmacol. 11 (1997) 379-393
4. Lefkowitz R.J. Historical review: a brief history and personal retrospective of seven-transmembrane receptors. Trends Pharmacol. Sci. 25 (2004) 413-422
5. Ariens E.J., and De Groot W.M. Affinity and intrinsic-activity in the theory of competitive inhibition. III. Homologous decamethonium-derivatives and succinyl-choline-esters. Arch. Int. Pharmacodyn. Ther. 99 (1954) 193-205
6. Chidiac P., et al. Inverse agonist activity of beta-adrenergic antagonists. Mol. Pharmacol. 45 (1994) 490-499
7. Samama P., et al. Negative antagonists promote an inactive conformation of the beta 2-adrenergic receptor. Mol. Pharmacol. 45 (1994) 390-394
8. Bond R.A., and Ijzerman A.P. Recent developments in constitutive receptor activity and inverse agonism, and their potential for GPCR drug discovery. Trends Pharmacol. Sci. 27 (2006) 92-96
9. Milligan G. Constitutive activity and inverse agonists of G protein-coupled receptors: a current perspective. Mol. Pharmacol. 64 (2003) 1271-1276
10. Hermans E. Biochemical and pharmacological control of the multiplicity of coupling at G-protein-coupled receptors. Pharmacol. Ther. 99 (2003) 25-44
11. Laugwitz K.L., et al. The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families. Proc. Natl. Acad. Sci. U. S. A. 93 (1996) 116-120
12. Brady A.E., and Limbird L.E. G protein-coupled receptor interacting proteins: emerging roles in localization and signal transduction. Cell. Signal. 14 (2002) 297-309
13. Bockaert J., et al. GPCR interacting proteins (GIP). Pharmacol. Ther. 103 (2004) 203-221
14. Dewire S.M., et al. beta-Arrestins and Cell Signaling. Annu. Rev. Physiol. 69 (2007) 483-510
15. Brink C.B., et al. Agonist-directed trafficking of porcine alpha(2A)-adrenergic receptor signaling in Chinese hamster ovary cells: l-isoproterenol selectively activates G(s). J. Pharmacol. Exp. Ther. 294 (2000) 539-547
16. Berg K.A., et al. Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus. Mol. Pharmacol. 54 (1998) 94-104
17. Spengler D., et al. Differential signal transduction by five splice variants of the PACAP receptor. Nature 365 (1993) 170-175
18. Gay E.A., et al. Functional selectivity of D2 receptor ligands in a Chinese hamster ovary hD2L cell line: evidence for induction of ligand-specific receptor states. Mol. Pharmacol. 66 (2004) 97-105
19. Shoemaker J.L., et al. Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors. J. Pharmacol. Exp. Ther. 315 (2005) 828-838
20. Kurrasch-Orbaugh D.M., et al. Serotonin 5-hydroxytryptamine 2A receptor-coupled phospholipase C and phospholipase A2 signaling pathways have different receptor reserves. J. Pharmacol. Exp. Ther. 304 (2003) 229-237
21. McLaughlin J.N., et al. Functional selectivity of G protein signaling by agonist peptides and thrombin for the protease-activated receptor-1. J. Biol. Chem. 280 (2005) 25048-25059
22. Hall D.A., et al. Signalling by CXC-chemokine receptors 1 and 2 expressed in CHO cells: a comparison of calcium mobilization, inhibition of adenylyl cyclase and stimulation of GTPgammaS binding induced by IL-8 and GROalpha. Br. J. Pharmacol. 126 (1999) 810-818
23. Moniri N.H., et al. Ligand-directed functional heterogeneity of histamine H1 receptors: novel dual-function ligands selectively activate and block H1-mediated phospholipase C and adenylyl cyclase signaling. J. Pharmacol. Exp. Ther. 311 (2004) 274-281
24. Krueger K.M., et al. G protein-dependent pharmacology of histamine H3 receptor ligands: evidence for heterogeneous active state receptor conformations. J. Pharmacol. Exp. Ther. 314 (2005) 271-281
25. Eason M.G., and Liggett S.B. Chimeric mutagenesis of putative G-protein coupling domains of the alpha2A-adrenergic receptor. Localization of two redundant and fully competent gi coupling domains. J. Biol. Chem. 271 (1996) 12826-12832
26. Kenakin T. Ligand-selective receptor conformations revisited: the promise and the problem. Trends Pharmacol. Sci. 24 (2003) 346-354
27. Kenakin T. Agonist-receptor efficacy. II. Agonist trafficking of receptor signals. Trends Pharmacol. Sci. 16 (1995) 232-238
28. Jarpe M.B., et al. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]Substance P acts as a biased agonist toward neuropeptide and chemokine receptors. J. Biol. Chem. 273 (1998) 3097-3104
29. Urban J.D., et al. Functional selectivity and classical concepts of quantitative pharmacology. J. Pharmacol. Exp. Ther. 320 (2007) 1-13
30. Azzi M., et al. Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 11406-11411
31. Gbahou F., et al. Protean agonism at histamine H3 receptors in vitro and in vivo. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 11086-11091
32. Baker J.G., et al. Agonist and inverse agonist actions of beta-blockers at the human beta 2-adrenoceptor provide evidence for agonist-directed signaling. Mol. Pharmacol. 64 (2003) 1357-1369
33. Audet N., et al. Internalization and Src activity regulate the time course of ERK activation by delta opioid receptor ligands. J. Biol. Chem. 280 (2005) 7808-7816
34. Werry T.D., et al. Characterization of serotonin 5-HT2C receptor signaling to extracellular signal-regulated kinases 1 and 2. J. Neurochem. 93 (2005) 1603-1615
35. Galandrin S., and Bouvier M. Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy. Mol. Pharmacol. 70 (2006) 1575-1584
36. Gether U., et al. Fluorescent labeling of purified beta 2 adrenergic receptor. Evidence for ligand-specific conformational changes. J. Biol. Chem. 270 (1995) 28268-28275
37. Ghanouni P., et al. Functionally different agonists induce distinct conformations in the G protein coupling domain of the beta 2 adrenergic receptor. J. Biol. Chem. 276 (2001) 24433-24436
38. Vilardaga J.P., et al. Molecular basis of inverse agonism in a G protein-coupled receptor. Nat. Chem. Biol. 1 (2005) 25-28
39. Hoffmann C., et al. A FlAsH-based FRET approach to determine G protein-coupled receptor activation in living cells. Nat. Methods 2 (2005) 171-176
40. Gales C., et al. Real-time monitoring of receptor and G-protein interactions in living cells. Nat. Methods 2 (2005) 177-184
41. Gales C., et al. Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes. Nat. Struct. Mol. Biol. 13 (2006) 778-786
42. Allouche S., et al. Differential G-protein activation by alkaloid and peptide opioid agonists in the human neuroblastoma cell line SK-N-BE. Biochem. J. 342 (1999) 71-78
43. Mukhopadhyay S., and Howlett A.C. Chemically distinct ligands promote differential CB1 cannabinoid receptor-Gi protein interactions. Mol. Pharmacol. 67 (2005) 2016-2024
44. Cussac D., et al. Differential activation of Gq/11 and Gi(3) proteins at 5-hydroxytryptamine(2C) receptors revealed by antibody capture assays: influence of receptor reserve and relationship to agonist-directed trafficking. Mol. Pharmacol. 62 (2002) 578-589
45. Gazi L., et al. 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. Br. J. Pharmacol. 138 (2003) 775-786
46. Stanasila L., et al. Coupling efficacy and selectivity of the human mu-opioid receptor expressed as receptor-Galpha fusion proteins in Escherichia coli. J. Neurochem. 75 (2000) 1190-1199
47. Clark M.J., et al. 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. 317 (2006) 858-864
48. Lauckner J.E., et al. The cannabinoid agonist WIN55,212-2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 19144-19149
49. Cordeaux Y., et al. Agonist regulation of D(2) dopamine receptor/G protein interaction. Evidence for agonist selection of G protein subtype. J. Biol. Chem. 276 (2001) 28667-28675
50. Watson C., et al. The use of stimulus-biased assay systems to detect agonist-specific receptor active states: implications for the trafficking of receptor stimulus by agonists. Mol. Pharmacol. 58 (2000) 1230-1238
51. MacKinnon A.C., et al. Bombesin and substance P analogues differentially regulate G-protein coupling to the bombesin receptor. Direct evidence for biased agonism. J. Biol. Chem. 276 (2001) 28083-28091
52. Wenzel-Seifert K., and Seifert R. Molecular analysis of beta(2)-adrenoceptor coupling to G(s)-, G(i)-, and G(q)-proteins. Mol. Pharmacol. 58 (2000) 954-966
53. Wei H., et al. Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 10782-10787
54. Charest P.G., et al. The V2 vasopressin receptor stimulates ERK1/2 activity independently of heterotrimeric G protein signalling. Cell. Signal. 19 (2007) 32-41
55. Gesty-Palmer D., et al. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J. Biol. Chem. 281 (2006) 10856-10864
56. Kenakin T. New concepts in drug discovery: collateral efficacy and permissive antagonism. Nat. Rev. Drug Discov. 4 (2005) 919-927
57. Thomas W.G., et al. Agonist-induced phosphorylation of the angiotensin II (AT(1A)) receptor requires generation of a conformation that is distinct from the inositol phosphate-signaling state. J. Biol. Chem. 275 (2000) 2893-2900
58. Stout B.D., et al. Rapid desensitization of the serotonin(2C) receptor system: effector pathway and agonist dependence. J. Pharmacol. Exp. Ther. 302 (2002) 957-962
59. Blake A.D., et al. Differential opioid agonist regulation of the mouse mu opioid receptor. J. Biol. Chem. 272 (1997) 782-790
60. Chakrabarti S., et al. Distinct differences between morphine- and [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin-mu-opioid receptor complexes demonstrated by cyclic AMP-dependent protein kinase phosphorylation. J. Neurochem. 71 (1998) 231-239
61. Kohout T.A., et al. Differential desensitization, receptor phosphorylation, beta-arrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7. J. Biol. Chem. 279 (2004) 23214-23222
62. Vigna S.R. The N-terminal domain of substance P is required for complete homologous desensitization but not phosphorylation of the rat neurokinin-1 receptor. Neuropeptides 35 (2001) 24-31
63. Whistler J.L., and von Zastrow M. Morphine-activated opioid receptors elude desensitization by beta-arrestin. Proc. Natl. Acad. Sci. U. S. A. 95 (1998) 9914-9919
64. Simmons M.A. Functional selectivity of NK1 receptor signaling: peptide agonists can preferentially produce receptor activation or desensitization. J. Pharmacol. Exp. Ther. 319 (2006) 907-913
65. Gray J.A., and Roth B.L. Paradoxical trafficking and regulation of 5-HT(2A) receptors by agonists and antagonists. Brain Res. Bull. 56 (2001) 441-451
66. Roettger B.F., et al. Antagonist-stimulated internalization of the G protein-coupled cholecystokinin receptor. Mol. Pharmacol. 51 (1997) 357-362
67. Bhowmick N., et al. The endothelin subtype A receptor undergoes agonist- and antagonist-mediated internalization in the absence of signaling. Endocrinology 139 (1998) 3185-3192
68. Sneddon W.B., et al. Activation-independent parathyroid hormone receptor internalization is regulated by NHERF1 (EBP50). J. Biol. Chem. 278 (2003) 43787-43796
69. Pheng L.H., et al. Agonist- and antagonist-induced sequestration/internalization of neuropeptide Y Y1 receptors in HEK293 cells. Br. J. Pharmacol. 139 (2003) 695-704
70. Vila-Coro A.J., et al. Characterization of RANTES- and aminooxypentane-RANTES-triggered desensitization signals reveals differences in recruitment of the G protein-coupled receptor complex. J. Immunol. 163 (1999) 3037-3044
71. Nickolls S.A., et al. Functional selectivity of melanocortin 4 receptor peptide and nonpeptide agonists: evidence for ligand-specific conformational states. J. Pharmacol. Exp. Ther. 313 (2005) 1281-1288
72. Breit A., et al. The natural inverse agonist agouti-related protein induces arrestin-mediated endocytosis of melanocortin-3 and -4 receptors. J. Biol. Chem. 281 (2006) 37447-37456
73. Kenakin T. Drug efficacy at G protein-coupled receptors. Annu. Rev. Pharmacol. Toxicol. 42 (2002) 349-379
74. Pierce K.L., et al. New mechanisms in heptahelical receptor signaling to mitogen activated protein kinase cascades. Oncogene 20 (2001) 1532-1539
75. Whistler J.L., et al. Functional dissociation of mu opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction. Neuron 23 (1999) 737-746
76. Zhang Y., et al. Allosteric potentiators of metabotropic glutamate receptor subtype 5 have differential effects on different signaling pathways in cortical astrocytes. J. Pharmacol. Exp. Ther. 315 (2005) 1212-1219
77. Nolan J.P., and Mandy F. Multiplexed and microparticle-based analyses: quantitative tools for the large-scale analysis of biological systems. Cytometry A 69 (2006) 318-325
78. Waller A., et al. Techniques: GPCR assembly, pharmacology and screening by flow cytometry. Trends Pharmacol. Sci. 25 (2004) 663-669
79. Kunkel E.J., et al. Rapid structure-activity and selectivity analysis of kinase inhibitors by BioMAP analysis in complex human primary cell-based models. Assay Drug Dev. Technol. 2 (2004) 431-441
80. Kunkel E.J., et al. An integrative biology approach for analysis of drug action in models of human vascular inflammation. FASEB J. 18 (2004) 1279-1281
81. Kobilka B.K., and Gether U. Use of fluorescence spectroscopy to study conformational changes in the beta 2-adrenoceptor. Methods Enzymol. 343 (2002) 170-182