Allosteric modulation of G protein-coupled receptors

Current Pharmaceutical Design

Volumn 10, Issue 17, 2004, Pages 2003-2013

  May, L T ^a   Avlani, V A ^a   Sexton, P M ^a   Christopoulos, Arthur ^a  

^a UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Allosteric interaction; Cooperativity; Dissociation kinetics; G protein coupled receptor; High throughput screening; Mathematical modeling; Radioligand binding; Ternary complex model

Indexed keywords

2 AMINO 6 BENZYL 3 (4 CHLOROBENZOYL) 4,5,6,7 TETRAHYDROTHIENO[2,3 C]PYRIDINE; 4 ANILINO 2 CYCLOPENTYLIMIDAZO[4,5 C]QUINOLINE; 8 CYCLOPENTYL 1,3 DIPROPYLXANTHINE; ACETYLSALICYLIC ACID; ADENOSINE RECEPTOR AFFECTING AGENT; AGMATINE; AMILORIDE DERIVATIVE; AMINO ACID RECEPTOR BLOCKING AGENT; BENZODIAZEPINE DERIVATIVE; CGP 13501; CGP 7930; DOPAMINE RECEPTOR AFFECTING AGENT; DU 116948; ENDOTHELIN RECEPTOR AFFECTING AGENT; FENDILINE; G PROTEIN COUPLED RECEPTOR; GABAERGIC RECEPTOR AFFECTING AGENT; GS 3783; GUANINE NUCLEOTIDE BINDING PROTEIN; LIGAND; N (2,3 DIPHENYL 1,2,4 THIADIAZOL 5(2H) YLIDENE)METHANAMINE; PB 81723; PRENYLAMINE; PROLYLLEUCYLGLYCINAMIDE; RECEPTOR BLOCKING AGENT; SALICYLATE SODIUM; SNAIL VENOM; UNCLASSIFIED DRUG; UNINDEXED DRUG; VU 5455; VU 8504; ZINC;

ALLOSTERISM; ANALYTIC METHOD; BINDING SITE; CELL ASSAY; DRUG MECHANISM; DRUG SAFETY; DRUG SCREENING; DRUG SELECTIVITY; DRUG TARGETING; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN GENOME; MODULATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; RECEPTOR BINDING; REVIEW;

ALLOSTERIC REGULATION; ANIMALS; HUMANS; LIGANDS; RADIOLIGAND ASSAY; RECEPTORS, G-PROTEIN-COUPLED;

EID: 3042557815     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/1381612043384303     Document Type: Review

References (57)

1. Fredriksson R, Lagerstrom MC, Lundin LG, Schioth HB. The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol 2003; 63: 1256-72.
2. Bourne HR. How receptors talk to trimeric G proteins. Curr Opin Cell Biol 1997; 9: 134-42.
3. Hamm HE. The many faces of G protein signaling. J Biol Chem 1998; 273: 669-72.
4. Drews J. Drug discovery: a historical perspective. Science 2000; 287: 1960-4.
5. Christopoulos A. Allosteric binding sites on cell-surface receptors: novel targets for drug discovery. Nat Rev Drug Discov 2002; 1: 198-210.
6. Christopoulos A, Kenakin TG. Protein-coupled receptor allosterism and complexing. Pharmacol Rev 2002; 54: 323-74.
7. Monod J, Changeux J-P, Jacob F. Allosteric proteins and cellular control systems. J Mol Biol 1963; 6: 306-29.
8. Monod J, Wyman J, Changeux J-P. On the nature of allosteric transitions: A plausible model. J Mol Biol 1965; 12: 88-118.
9. Colquhoun D. Binding, gating, affinity and efficacy: The interpretation of structure-activity relationships for agonists and of the effects of mutating receptors. Brit J Pharmacol 1998; 125: 924-47.
10. Neubig RR, Spedding M, Kenakin T, Christopoulos A. International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on Terms and Symbols in Quantitative Pharmacology. Pharmacol Rev 2003; 55: 597-606.
11. Stockton JM, Birdsall NJM, Burgen ASV, Hulme EC. Modification of the binding properties of muscarinic receptors by gallamine. Mol Pharmacol 1983; 23: 551-7.
12. Ehlert FJ. Estimation of the affinities of allosteric ligands using radioligand binding and pharmacological null methods. Mol Pharmacol 1988; 33: 187-94.
13. Lazareno S, Birdsall NJM. Detection, quantitation, and verification of allosteric interactions of agents with labeled and unlabeled ligands at G protein-coupled receptors: interactions of strychnine and acetylcholine at muscarinic receptors. Mol Pharmacol 1995; 48: 362-78.
14. De Lean A, Stadel JM, Lefkowitz RJ. A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled β-adrenergic receptor. J Biol Chem 1980; 255: 7108-17.
15. Ehlert FJ. The relationship between muscarinic receptor occupancy and adenylate cyclase inhibition in the rabbit myocardium. Mol Pharmacol 1985; 28: 410-21.
16. Birdsall NJM, Lazareno, S. Allosterisin at muscarinic receptors: ligands and mechanisms. Mini-Rev Med Chem 2004; In Press.
17. Jakubik J, Bacakova L, Lisa V, El-Fakahany EE, Tucek S. Activation of muscarinic acetylcholine receptors via their allosteric binding sites. Proc Natl Acad Sci USA 1996; 93: 8705-9.
18. Thomas EA, Carson MJ, Neal MJ, Sutcliffe JG. Unique allosteric regulation of 5-hydroxytryptamine receptor-mediated signal transduction by oleamide. Proc Natl Acad Sci USA 1997; 94: 14115-9.
19. Zahn K, Eckstein N, Trankle C, Sadee W, Mohr K. Allosteric modulation of muscarinic receptor signaling: alcuronium- induced conversion of pilocarpine from an agonist into an antagonist. J Pharmacol Exp Ther 2002; 301: 720-8.
20. Litschig S, Gasparini F, Rueegg D, Stoehr N, Flor PJ, Vranesic I, et al. CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signaling without affecting glutamate binding. Mol Pharmacol 1999; 55: 453-61.
21. Pagano A, Ruegg D, Litschig S, Stoehr N, Stierlin C, Heinrich M, et al. The non-competitive antagonists 2-methyl-6-(phenylethynyl) pyridine and 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester interact with overlapping binding pockets in the transmembrane region of group 1 metabotropic glutamate receptors. J Biol Chem 2000; 275: 33750-8.
22. Knoflach F, Mutel V, Jolidon S, Kew JN, Malherbe P, Vieira E, et al. Positive allosteric modulators of metabotropic glutamate 1 receptor: Characterization, mechanism of action, and binding site. Proc Natl Acad Sci USA 2001; 23: 13402-7.
23. Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W, et al. N,N′-Dicyclopentyl-2-methylsulfanyl-5-nitropyrimidine-4,6-diamine (GS39783) and structurally related compounds: novel allosteric enhancers of gamma-aminobutyric acidB receptor function. J Pharmacol Exp Ther 2003; 307: 322-30.
24. Sachpatzidis A, Benton BK, Manfredi JP, Wang H, Hamilton A, Dohlman HG, et al. Identification of allosteric Peptide agonists of CXCR4. J Biol Chem 2003; 278: 896-907.
25. Hall DA. Modeling the functional effects of allosteric modulators at pharmacological receptors: An extension of the two-state model of receptor activation. Mol Pharmacol 2000; 58: 1412-23.
26. Parmentier ML, Prezeau L, Bockaert J, Pin J. P. A model for the functioning of family 3 GPCRs. Trends Pharmacol Sci 2002; 23: 268-74.
27. Sharpe IA, Gehrmann J, Loughnan ML, Thomas L, Adams DA, Atkins A, et al. Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline transporter. Nat Neurosci 2001; 4: 902-7.
28. Sharpe IA, Thomas L, Loughnan M, Motin L, Palant E, Croker DE, et al. Allosteric alpha 1-adrenoreceptor antagonism by the conopeptide ρ-TIA. J Biol Chem 2003; 278: 34451-7.
29. Fawzi AB, Macdonald D, Benbow LL, Smith-Torhan A, Zhang H. Weig BC, et al. SCH-202676: An allosteric modulator of both agonist and antagonist binding to G protein-coupled receptors. Mol Pharmacol 2001; 59: 30-7.
30. 1 muscarinic acetylcholine receptors. J Pharmacol Exp Ther 2004; In Press.
31. Kollias-Baker CA, Ruble J, Jacobson M, Harrison JK, Ozeck M, Shryock JC, et al. Agonist-independent effect of an allosteric enhancer of the A1 adenosine receptor in CHO cells stably expressing the recombinant human A1 receptor. J Pharmacol Exp Ther 1997; 281: 761-8.
32. Kenakin TP. Pharmacologic Analysis of Drug-Receptor Interaction., Lippincott-Raven: Philadelphia, PA 1997.
33. Felder CC, Bymaster FP, Ward J, DeLapp N. Therapeutic opportunities for muscarinic receptors in the central nervous system. J Med Chem 2000; 43: 4333-53.
34. Wess J. Mutational analysis of muscarinic acetylcholine receptors: Structural basis of ligand/receptor/G protein interactions. Life Sci 1993; 53: 1447-63.
35. Ellis J, Huyler J, Brann MR. Allosteric regulation of cloned m1-m5 muscarinic receptor subtypes. Biochem Pharmacol 1991; 42: 1927-32.
36. Christopoulos A, Lanzafame A, Mitchelson F. Allosteric interactions at muscarinic cholinoceptors. Clin Exp Pharmacol Physiol 1998; 25: 184-94.
37. Ellis J. Allosteric binding sites on muscarinic receptors. Drug Dev Res 1997; 40: 193-204.
38. Pin JP, Galvez T, Prezeau L. Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol Ther 2003; 98: 325-54.
39. Hu J, Spiegel AM. Naturally occurring mutations of the extracellular Ca2+-sensing receptor: implications for its structure and function. Trends Endocrinol Metab 2003; 14: 282-8.
40. Malherbe P, Kratochwil N, Knotlach F, Zenner MT, Kew JN, Kratzeisen C, et al. Mutational analysis and molecular modeling of the allosteric binding site of a novel, selective, noncompetitive antagonist of the metabotropic glutamate 1 receptor. J Biol Chem 2003; 278: 8340-7.
41. Schaffhauser H, Rowe BA, Morales S, Chavez-Noriega LE, Yin R, Jachec C, et al. Pharmacological characterization and identification of amino acids involved in the positive modulation of metabotropic glutamate receptor subtype 2. Mol Pharmacol 2003; 64: 798-810.
42. Lazareno S, Gharagozloo P, Kuonen D, Popham A, Birdsall NJM. Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic recptors: Radioligand binding studies. Molecular Pharmacology 1998; 53: 573-89.
43. 4 Receptors: Receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol 2004; In Press.
44. Birdsall NJ, Farries T, Gharagozloo P, Kobayashi S, Kuonen D, Lazareno S, et al. Selective allosteric enhancement of the binding and actions of acetylcholine at muscarinic receptor subtypes. Life Sci 1997; 60: 1047-52.
45. Lutz M, Kenakin T. Quantitative Molecular Pharmacology And Informatics In Drug Discovery, Wiley: New York 1999.
46. Christopoulos A. In Enna, SJ Ed, Current Protocols In Pharmacology. NY, Wiley and Sons 2000; 1.22.1-40.
47. Kostenis E, Mohr K. Two-point kinetic experiments to quantify allosteric effects on radioligand dissociation. Trends Pharmacol Sci 1996; 17: 280-3.
48. Proska J, Tucek S. Mechanisms of steric and cooperative actions of alcuronium on cardiac muscarinic acetylcholine receptors. Mol Pharmacol 1994; 45: 709-17.
49. Avlani VA, May LT, Sexton PM, Christopoulos A. Application of a kinetic model to the apparently complex behaviors of negative and positive allosteric modulators of muscarinic acetylcholine receptors. J Pharmacol Exp Ther 2004; In Press.
50. 2 receptors. Mol Pharmacol 1998; 54: 139-45.
51. 3H]R214127: A Novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists. Mol Pharmacol 2003; 63: 1082-93.
52. Rees S, Morrow D, Kenakin T. GPCR drug discovery through the exploitation of allosteric drug binding sites. Receptors Channels 2002; 8: 261-8.
53. May LT, Christopoulos A. Allosteric modulators of G-protein-coupled receptors. Curr Opin Pharmacol 2003; 3: 551-6.
54. 2A-adrenergic receptor. Mol Pharmacol 1998; 53: 916-25.
55. Bleakman D, Gates MR, Ogden AM, Mackowiak M. Kainate receptor agonists, antagonists and allosteric modulators. Curr Pharm Design 2002; 8(10): 873-85.
56. Moro S, Jacobson KA. Molecular modeling as a tool to investigate molecular recognition in P2Y receptors. Curr Pharm Design 2002: 8(26): 2401-13.
57. Zimanyi IA, Pelleymounter MA. The role of melanocortin peptides and receptors in regulation of energy balance. Curr Pharm Design 2003; 9(8): 627-41.