Ligand-selective receptor conformations revisited: The promise and the problem

Trends in Pharmacological Sciences

Volumn 24, Issue 7, 2003, Pages 346-354

  Kenakin, Terry ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2,3 DIHYDRO 1 METHYL 2 OXO 5 PHENYL 1H 1,4 BENZODIAZEPIN 3 YL) 3 (3 METHYLPHENYL)UREA; ADRENERGIC RECEPTOR; ALPRENOLOL; ANGIOTENSIN 2 RECEPTOR; ANTIBODY MC1; ANTIBODY MC4; BOMBESIN RECEPTOR; CALCITONIN; CALCITONIN RECEPTOR; CANNABINOID RECEPTOR; CCR5 ANTIBODY; CHEMOKINE RECEPTOR; CHOLECYSTOKININ RECEPTOR BLOCKING AGENT; CHOLECYSTOKININ RECEPTOR STIMULATING AGENT; DELTORPHIN; DOBUTAMINE; DOPAMINE 2 RECEPTOR; ENKEPHALIN[2,5 DEXTRO PENICILLAMINE]; ETORPHINE; GUANINE NUCLEOTIDE BINDING PROTEIN; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE RECEPTOR; ISOPRENALINE; OPIATE RECEPTOR; PARATHYROID HORMONE; PARATHYROID HORMONE RECEPTOR; RB 213; RECEPTOR ANTIBODY; SALBUTAMOL; SEROTONIN RECEPTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; CELL SURFACE RECEPTOR; LIGAND;

DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; HUMAN; LIGAND BINDING; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN PHOSPHORYLATION; RECEPTOR AFFINITY; RECEPTOR BINDING; REVIEW; SIGNAL TRANSDUCTION; CHEMISTRY; DRUG DESIGN; DRUG POTENTIATION; GENETICS;

DRUG DESIGN; LIGANDS; RECEPTORS, CELL SURFACE;

EID: 0043235844     PISSN: 01656147     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0165-6147(03)00167-6     Document Type: Review

References (72)

1. Kenakin T.P. Agonist-receptor efficacy II: agonist-trafficking of receptor signals. Trends Pharmacol. Sci. 16:1995;232-238.
2. Kenakin T.P. Efficacy at G protein coupled receptors. Annu. Rev. Pharmacol. Toxicol. 42:2002;349-379.
3. Kenakin T.P. Efficacy at G protein coupled receptors. Nat. Rev. Drug Discov. 1:2002;103-109.
4. 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.
5. Hilser V.J., Freire E. Predicting the equilibrium protein folding pathway: structure-based analysis of staphylococcal nuclease. Proteins. 27:1997;171-183.
6. Hilser V.J., et al. The structural distribution of cooperative interactions in proteins: analysis of the native state ensemble. Proc. Natl. Acad. Sci. U. S. A. 95:1998;9903-9908.
7. Woodward C., et al. Hydrogen exchange and the dynamic structure of proteins. Mol. Cell. Biochem. 48:1982;135-141.
8. Woodward C. Is the slow-exchange core the protein folding core? Trends Biochem. Sci. 18:1993;359-360.
9. 1B-adrenergic receptor by all amino acid substitutions at a single site. J. Biol. Chem. 267:1992;1430-1433.
10. Samama P., et al. A mutation-induced activated state of the β2-adrenergic receptor: extending the ternary complex model. J. Biol. Chem. 268:1993;4625-4636.
11. Weiss J.M., et al. The cubic ternary complex receptor-occupancy model. I. Model description. J. Theor. Biol. 178:1996;151-167.
12. Weiss J.M., et al. The cubic ternary complex receptor-occupancy model. II. Understanding apparent affinity. J. Theor. Biol. 178:1996;169-182.
13. Weiss J.M., et al. The cubic ternary complex receptor-occupancy model. III. Resurrecting efficacy. J. Theor. Biol. 181:1996;381-397.
14. Burgen A.S.V. Conformational changes and drug action. Fed. Proc. 40:1966;2723-2728.
15. Kenakin T.P. Receptor conformational induction vs. selection: all part of the same energy landscape. Trends Pharmacol. Sci. 17:1996;190-191.
16. 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.
17. Allouche S., et al. Differential G-protein activation by alkaloid and peptide agonists in the human neuroblastoma cell line SKE-N-BE. Biochem. J. 342:1999;71-78.
18. Kenakin T.P. Protean agonists: keys to receptor active state? Ann. N. Y. Acad. Sci. 812:1997;116-125.
19. Pommier B., et al. The cholecystokinB receptor is coupled to two effector pathways through pertussis toxin-sensitive and -insensitive G proteins. J. Neurochem. 73:1999;281-288.
20. Stephenson R.P. A modification of receptor theory. Br. J. Pharmacol. 11:1956;379-393.
21. Brady A.E., Limbird L.E. G protein-coupled receptor interacting proteins: emerging roles in localization and signal transduction. Cell. Signal. 14:2002;297-309.
22. Kenakin T.P. Inverse, protean, and ligand-selective agonism: matters of receptor conformation. FASEB J. 15:2001;598-611.
23. Blanpain C., et al. Multiple active states and oligermization of CCR5 revealed by functional properties of monoclonal antibodies. Mol. Biol. Cell. 13:2002;723-737.
24. Christopoulos A., Kenakin T.P. G-protein coupled receptor allosterism and complexing. Pharmacol. Rev. 54:2002;323-372.
25. Gether U., et al. Fluorescent labeling of purified β2-adrenergic receptor: evidence for ligand specific conformational changes. J. Biol. Chem. 270:1995;28268-28275.
26. Baba M., et al. A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc. Natl. Acad. Sci. U. S. A. 96:1999;5698-5703.
27. Finke P.E., et al. Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4: synthesis and structure-Activity relationships for 1-[N-(Methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl) -N-(benzyloxycarbonyl)amino)piperidin-1-yl)butanes. Bioorg. Med. Chem. Lett. 11:2001;2475-2479.
28. Strizki J.M., et al. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc. Natl. Acad. Sci. U. S. A. 98:2001;12718-12723.
29. Wells T.N.C., et al. Chemokine receptors-the new frontier for aids research. Chem. Biol. 3:1996;603-609.
30. MacKinnon A.C., et al. Bombesin and substance P analogues differentially regulate G-protein coupling to the bombesin receptor. J. Biol. Chem. 276:2001;28083-28091.
31. Takasu H., et al. Amino-terminal modifications of human parathyroid hormone (PTH) selectively alter phospholipase C signaling via type 1 PTH receptor: Implications for design of signal-specific PTH ligands. Biochemistry. 38:1999;13453-13460.
32. Kenakin T.P. Agonist selective receptor states: the new level of selectivity? Pharm. News. 5:1998;20-25.
33. αi/o-proteins. Mol. Pharmacol. 61:2002;85-96.
34. Kenakin T.P. Recombinant roulette versus the apparent virtues of 'natural' cell receptor systems: receptor genotypes vs phenotypes. Trends Pharmacol. Sci. 23:2002;403-404.
35. Spengler D., et al. Differential signal transduction by five splice variants of the PACAP receptor. Nature. 365:1993;170-175.
36. Rampelbergh A., et al. Properties of the pituitary adenylate cyclase-activating polypeptide I and II receptors, vasoactive intestinal peptide1, and chimeric amino- terminal pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide1 receptors: evidence for multiple receptor states. Mol. Pharmacol. 50:1996;1596-1604.
37. Meller E., et al. Comparative effects of receptor inactivation, 17β-estradiol and pertussis toxin on dopaminergic inhibition of prolactin-secretion in vitro. J. Pharmacol. Exp. Ther. 263:1992;462-469.
38. Mottola D.M., et al. Functional selectivity of dopamine receptor agonists. I. Selective activation of postsynaptic dopamine D-1 receptors linked to adenylate cyclase. J. Pharmacol. Exp. Ther. 301:2002;1166-1178.
39. Robb S., et al. Agonist-specific coupling of a cloned Drosophila octopamine/tyramine receptor to multiple second messenger systems. EMBO J. 13:1994;1325-1330.
40. 11]SP analogues. J. Biol. Chem. 274:1999;23770- 23776.
41. Wenzel-Seifert K., Seifert R. Molecular analysis of β2-adrenoceptor coupling to Gs-, Gi-, and Gq- proteins. Mol. Pharmacol. 58:2000;954-966.
42. i/1o activation profiles in CHO cells expressing human muscarinic acetylcholine receptors: Dependence on agonist as well as receptor-subtype. Br. J. Pharmacol. 132:2001;950-958.
43. Cordeaux Y., et al. Influence of receptor number on funcitonal responses elicited by agonists acting at the human adenosine A1 receptor: evidence for signaling pathway-dependent changes in agonist potency and relative intrinsic activity. Mol. Pharmacol. 58:2000;1075-1084.
44. 2A-adrenoceptor responses in HEL 92.1.7 cells. Br. J. Pharmacol. 132:2001;1477-1484.
45. MacKinnon A.C., et al. Bombesin and substance P analogues differentially regulate G-protein coupling to the bombesin receptor. J. Biol. Chem. 276:2001;28083-28091.
46. 2A receptors are labeled by agonists and discriminated by antagonists. Mol. Pharmacol. 60:2001;690-699.
47. Bonhaus D.W., et al. Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: evidence for agonist-specific trafficking of intracellular process. J. Pharmacol. Exp. Ther. 287:1998;884-888.
48. 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 GTPS binding induced by IL-8 and GROα Br. J. Pharmacol. 126:1999;810-818.
49. Berg K.A., et al. Effect 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.
50. 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.
51. Chidiac P., et al. Inverse agonist activity of β-adrenergic antagonists. Mol. Pharmacol. 45:1994;490-499.
52. 2-adrenergic receptor. Mol. Pharmacol. 50:1996;662-666.
53. 2A- adrenoceptors. Mol. Pharmacol. 53:1998;963-968.
54. Pauwells P.J. Evidence for protean agonism of RX 831003 at a2A-adrenoceptors by co-expression with different Ga protein subunits. Neurophamacology. 42:2002;855-863.
55. Fathy D.B., et al. Spontaneous human B2 bradykinin receptor activity determines the action of partial agonists as agonists or inverse agonists. J. Biol. Chem. 274:1999;29603-29606.
56. 2+ current in mouse venturicular myocytes. Mol. Pharmacol. 56:1999;485-493.
57. Wiens B.L., et al. Contribution of serine residues to constitutive and agonist-induced signaling via the D2s dopamine receptor: evidence for multiple, agonist-specific active conformations. Mol. Pharmacol. 54:1998;435-444.
58. 5]enkephalin. J. Biol. Chem. 276:2001;37779-37786.
59. Dunlop A., et al. Characterization of 5-HT1A receptor functional coupling in cells expressing the human 5-HT1A receptor as assessed with the cytosensor microphysiometer. J. Pharmacol. Toxicol. Meth. 40:1999;47-55.
60. Konkar B., et al. Aryloxypropanolamine and catecholamine ligand interactions with the β1-adrenergic receptor: evidence for interaction with distinct conformations of β1-adrenergic receptors. J. Pharmacol. Exp. Ther. 294:2000;923-932.
61. Roettger B.F., et al. Antagonist-stimulated internalization of the G protein-coupled cholecystokinin receptor. Mol. Pharmacol. 51:1997;357-362.
62. Keith D.E., et al. Morphine activates opioid receptors without causing their rapid internalization. J. Biol. Chem. 271:1996;19021-19024.
63. Hunyady L., et al. Independence of type I angiotensin II receptor endocytosis from G protein coupling and signal transduction. J. Biol. Chem. 269:1994;24798-24804.
64. 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.
65. Mack M., et al. Aminooxypentane-RANTES induces CCR5 internalization but inhibits recycling: a novel inhibitory mechanism of HIV infectivity. J. Exp. Med. 187:1998;1215-1224.
66. Bisello A., et al. Selective ligand-induced stabilization of active and desensitized parathyroid hormone type 1 receptor conformations. J. Biol. Chem. 277:2002;38524-38530.
67. Thomas W.G., et al. Agonist-induced phosphorylation of the angiotensin II (AT1A) receptor requires generation of a conformation that is distinct from the inositol phosphate-signaling state. J. Biol. Chem. 275:2000;2893-2900.
68. 5]enkephalin-mu- opioid complexes demonstrated by cyclic independent protein kinase phosphorylation. J. Neurochem. 71:1998;231-239.
69. Blake A.D., et al. Differential opioid agonist regulation of the mouse μ opioid receptor. J. Biol. Chem. 272:1997;782-790.
70. van Hooft J.A., Vijverberg H.P.M. Selection of distinct conformational states of the 5-HT3 receptor by full and partial agonists. Br. J. Pharmacol. 117:1996;839-846.
71. s complex: evidence for agonist-specific states. Mol. Pharmacol. 52:1997;144-154.
72. s interactions: evidence for multiple receptor conformations. Mol. Pharmacol. 56:1999;348-358.