Allosteric modulation of G-protein coupled receptors

European Journal of Pharmaceutical Sciences

Volumn 21, Issue 4, 2004, Pages 407-420

  Jensen, Anders A ^a   Spalding, Tracy A ^b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b ACADIA PHARMACEUTICALS INC   (United States)

Author keywords

Allosteric modulation; Allosteric modulator; G protein coupled receptors (GPCRs); Inhibition; Potentiation

Indexed keywords

2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; ALCURONIUM; ALKANE DERIVATIVE; AMMONIUM DERIVATIVE; BAY 36720; BAY 367620; G PROTEIN COUPLED RECEPTOR; GALLAMINE; KT 5720; LIGAND; LY 487379; LY 487397; NPS 2390; NPSR 467; NPSR 568; PROTEIN INHIBITOR; R 214127; R 314127; R 314217; RO 016128; RO 645229; RO 677476; UNCLASSIFIED DRUG; WIN 62577;

ALLOSTERISM; COMBINATORIAL CHEMISTRY; CONTROLLED STUDY; DRUG POTENTIATION; HUMAN; HUMAN CELL; ION TRANSPORT; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN FAMILY; RECEPTOR BINDING; SHORT SURVEY; SIGNAL TRANSDUCTION;

EID: 1442284465     PISSN: 09280987     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejps.2003.11.007     Document Type: Review

References (107)

1. Alberts G.L., Chio C.L., Im W.B. Allosteric modulation of the human 5-HT7A receptor by lipidic amphipathic compounds. Mol. Pharmacol. 60:2001;1349-1355.
2. Angers S., Salahpour A., Bouvier M. Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function. Annu. Rev. Pharmacol. Toxicol. 42:2002;409-435.
3. Bailey, 2001. Patent status of the therapeutically important G-protein-coupled receptors. Expert Opin. Ther. Patents 11, 1861-1887.
4. Birdsall N.J., Farries T., Gharagozloo P., Kobayashi S., Kuonen D., Lazareno S., Popham A., Sugimoto M. Selective allosteric enhancement of the binding and actions of acetylcholine at muscarinic receptor subtypes. Life Sci. 60:1997;1047-1052.
5. Birdsall N.J., Farries T., Gharagozloo P., Kobayashi S., Lazareno S., Sugimoto M. Subtype-selective positive co-operative interactions between brucine analogs and acetylcholine at muscarinic receptors: functional studies. Mol. Pharmacol. 55:1999;778-786.
6. Buller S., Zlotos D.P., Mohr K., Ellis J. Allosteric site on muscarinic acetylcholine receptors: a single amino acid in transmembrane region 7 is critical to the subtype selectivities of caracurine V derivatives and alkane-bisammonium ligands. Mol. Pharmacol. 61:2002;160-168.
7. Carroll F.Y., Stolle A., Beart P.M., Voerste A., Brabet I., Mauler F., Joly C., Antonicek H., Bockaert J., Müller T., Pin J., Prézeau L. BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse agonist activity. Mol. Pharmacol. 59:2001;965-973.
8. Christopoulos A., Kenakin T. G protein-coupled receptor allosterism and complexing. Pharmacol. Rev. 54:2002;323-374.
9. Clark A.L., Mitchelson F. The inhibitory effect of gallamine on muscarinic receptors. Br. J. Pharmacol. 58:1976;323-331.
10. 2+-sensing receptor. Proc. Natl. Acad. Sci. U.S.A. 97:2000;4814-4819.
11. Costa T., Herz A. Antagonists with negative intrinsic activity at d opioid receptors coupled to GTP-binding proteins. Proc. Natl. Acad. Sci. U.S.A. 86:1989;7321-7325.
12. El Far O., Betz H. G-protein-coupled receptors for neurotransmitter amino acids: C-terminal tails, crowded signalosomes. Biochem. J. 365:2002;329-336.
13. Elling C.E., Thirstrup K., Holst B., Schwartz T.W. Conversion of agonist site to metal-ion chelator site in the β2-adrenergic receptor. Proc. Natl. Acad. Sci. U.S.A. 96:1999;12322-12327.
14. Ellis J., Seidenberg M. Two allosteric modulators interact at a common site on cardiac muscarinic receptors. Mol. Pharmacol. 42:1992;638-641.
15. Ellis J., Seidenberg M. Interactions of alcuronium, TMB-8, and other allosteric ligands with muscarinic acetylcholine receptors: studies with chimeric receptors. Mol. Pharmacol. 58:2000;1451-1460.
16. Ellis J., Seidenberg M., Brann M.R. Use of chimeric muscarinic receptors to investigate epitopes involved in allosteric interactions. Mol. Pharmacol. 44:1993;583-588.
17. Fawzi A.B., Macdonald D., Benbow L.L., Smith-Torhan A., Zhang H., Weig B.C., Ho G., Tulshian D., Linder M.E., Graziano M.P. SCH-202676: an allosteric modulator of both agonist and antagonist binding to G protein-coupled receptors. Mol. Pharmacol. 59:2001;30-37.
18. 1B/1D receptors. Behav. Brain Res. 73:1996;313-317.
19. Frederickson C.J. Neurobiology of zinc and zinc-containing neurons. Int. Rev. Neurobiol. 31:1989;145-238.
20. Freissmuth M., Waldhoer M., Bofill-Cardona E., Nanoff C. G protein antagonists. Trends Pharmacol. Sci. 20:1999;237-245.
21. 2A adenosine receptors by amiloride analogues and sodium ions. Biochem. Pharmacol. 60:2000;669-676.
22. 3 adenosine receptors by a series of 3-(2-pyridinyl)isoquinoline derivatives. Mol. Pharmacol. 60:2001;1057-1063.
23. 3 adenosine receptor. Mol. Pharmacol. 63:2003;1021-1031.
24. Gether U. Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr. Rev. 21:2000;90-113.
25. Gnagey A.L., Seidenberg M., Ellis J. Site-directed mutagenesis reveals two epitopes involved in the subtype selectivity of the allosteric interactions of gallamine at muscarinic acetylcholine receptors. Mol. Pharmacol. 56:1999;1245-1253.
26. Hall D.A. Modelling the functional effects of allosteric modulators at pharmacological receptors: an extension of the two-state model of receptor activation. Mol. Pharmacol. 58:2000;1412-1423.
27. 2+ receptor expressed in Xenopus laevis oocytes by NPS 467 or NPS 568. Mol. Pharmacol. 53:1998;1083-1088.
28. 2+ receptors. Mol. Pharmacol. 55:1999;642-648.
29. 2 dopamine receptors by amiloride and amiloride analogues. Mol. Pharmacol. 50:1996;1295-1308.
30. Hohenegger M., Waldhoer M., Beindl W., Boing B., Kreimeyer A., Nickel P., Nanoff C., Freissmuth M. Gsα-selective G protein antagonists. Proc. Natl. Acad. Sci. U.S.A. 95:1998;346-351.
31. Holst B., Elling C.E., Schwartz T.W. Partial agonism through a zinc-ion switch constructed between transmembrane domains III and VII in the tachykinin NK1 receptor. Mol. Pharmacol. 58:2000;263-270.
32. Holst B., Elling C.E., Schwartz T.W. Metal-ion mediated agonism and agonist-enhancement in the melanocortin MC1 and MC4 receptors. J. Biol. Chem. 277:2002;47662-47670.
33. Horstman D.A., Brandon S., Wilson A.L., Guyer C.A., Cragoe E.J. Jr., Limbird L.E. An aspartate conserved among G-protein receptors confers allosteric regulation of α2-adrenergic receptors by sodium. J. Biol. Chem. 265:1990;21590-21595.
34. Hulme, E.C., Lu, Z.L., Bee, 2003. Scanning mutagenesis studies of the M1 muscarinic acetylcholine receptor. Receptors Channels 9, 215-228.
35. 2C receptor. Mol. Pharmacol. 64:2003;78-84.
36. Jakubik J., Bacakova L., Lisa V., el-Fakahany E.E., Tucek S. Activation of muscarinic acetylcholine receptors via their allosteric binding sites. Proc. Natl. Acad. Sci. U.S.A. 93:1996;8705-8709.
37. Jakubik J., Bacakova L., El-Fakahany E.E., Tucek S. Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol. Pharmacol. 52:1997;172-179.
38. Jensen A.A., Greenwood J.R., Bräuner-Osborne H. The dance of the clams: twists and turns in the family C GPCR homodimer. Trends Pharmacol. Sci. 23:2002;491-493.
39. Kenakin T. Ligand-selective receptor conformations revisited: the promise and the problem. Trends Pharmacol. Sci. 24:2003;346-354.
40. Knoflach F., Mutel V., Jolidon S., Kew J.N., Malherbe P., Vieira E., Wichmann J., Kemp J.A. Positive allosteric modulators of metabotropic glutamate 1 receptor: characterization, mechanism of action, and binding site. Proc. Natl. Acad. Sci. U.S.A. 98:2001;13402-13407.
41. Kohl B.K., Dannhardt G. The NMDA receptor complex: a promising target for novel antiepileptic strategies. Curr. Med. Chem. 8:2001;1275-1289.
42. Kollias-Baker C.A., Ruble J., Jacobson M., Harrison J., Ozeck M., Shryock J.C., Belardinelli L. 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. 281:1997;761-768.
43. 3 receptors. Mol. Pharmacol. 60:2001;761-767.
44. 2+-sensing function of the metabotropic glutamate receptors. Science. 279:1998;1722-1725.
45. Kunishima N., Shimada Y., Tsuji Y., Sato T., Yamamoto M., Kumasaka T., Nakanishi S., Jingami H., Morikawa K. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature. 407:2000;971-976.
46. 3H ]R214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists Mol. Pharmacol. 63:2003;1082-1093.
47. Lazareno S., Gharagozloo P., Kuonen D., Popham A., Birdsall N.J. Subtype-selective positive co-operative interactions between brucine analogues and acetylcholine at muscarinic receptors: radioligand binding studies. Mol. Pharmacol. 53:1998;573-589.
48. 3H ]scopolamine and acetylcholine at muscarinic receptor subtypes: identification of a second allosteric site Mol. Pharmacol. 58:2000;194-207.
49. Lazareno S., Popham A., Birdsall N.J. Analogs of WIN62,577 define a second allosteric site on muscarinic receptors. Mol. Pharmacol. 62:2002;1492-1505.
50. Leff P. The two-state model of receptor activation. Trends Pharmacol. Sci. 16:1995;89-97.
51. 2A-adrenoceptor: allosteric modulation by amilorides. Mol. Pharmacol. 58:2000;1091-1099.
52. 1A-adrenergic receptor. Mol. Pharmacol. 57:2000;436-445.
53. Liang Y., Fotiadis D., Filipek S., Saperstein D.A., Palczewski K., Engel A. Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes. J. Biol. Chem. 278:2003;21655-21662.
54. Litschig S., Gasparini F., Rueegg D., Stoehr N., Flor P.J., Vranesic I., Prezeau L., Pin J.-P., Thomsen C., Kuhn R. CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signalling without affecting glutamate binding. Mol. Pharmacol. 55:1999;453-461.
55. Lüllmann H., Ohnesorge F.K., Schauwecker G.C., Wasserman O. Inhibition of the actions of carbachol and DFP on guinea pig isolated atria by alkane-bis ammonium compounds. Eur. J. Pharmacol. 6:1969;241-247.
56. Maj M., Bruno V., Dragic Z., Yamamoto R., Battaglia G., Inderbitzin W., Stoehr N., Stein T., Gasparini F., Vranesic I., Kuhn R., Nicoletti F., Flor P.J. (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection. Neuropharmacology. 45:2003;895-906.
57. Malherbe, P., Kratochwil, N., Knoflach, F., Zenner, M.T., Kew, J.N., Kratzeisen, C., Maerki, H.P., Adam, G., Mutel, V., 2003a. Mutational analysis and molecular modelling of the allosteric binding site of a novel, selective, non-competitive antagonist of the metabotropic glutamate 1 receptor. J. Biol. Chem. 278, 8340-8347.
58. Malherbe P., Kratochwil N., Zenner M.T., Piussi J., Diener C., Kratzeisen C., Fischer C., Porter R.H.P. Mutational analysis and molecular modelling of the binding pocket of the metabotropic glutamate 5 receptor negative modulator 2-methyl-6-(phenylethynyl)-pyridine. Mol. Pharmacol. 64:2003b;823-832.
59. Marino, M.J., William Jr., D.L., O'Brien, J.A., Valenti, O., McDonald, T.P., Clements, M.K., Wang, R., DiLella, A.G., Hess, J.F., Kinney, G.G., Conn, P.J., 2003. Allosteric modulation of group III metabotropic glutamate receptor 4: a potential approach to Parkinson's disease treatment. Proc. Natl. Acad. Sci. U.S.A. 100, 13668-13673.
60. Martin S., Botto J.M., Vincent J.P., Mazella J. Pivotal role of an aspartate residue in sodium sensitivity and coupling to G proteins of neurotensin receptors. Mol. Pharmacol. 55:1999;210-215.
61. 1B/1D receptors. Mol. Pharmacol. 50:1996;752-762.
62. Mathiesen J.M., Svendsen N., Bräuner-Osborne H., Thomsen C., Ramirez M.T. Positive allosteric modulation of human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP. Br. J. Pharmacol. 138:2003;1026-1030.
63. Matsui H., Lazareno S., Birdsall N.J. Probing of the location of the allosteric site on m1 muscarinic receptors by site-directed mutagenesis. Mol. Pharmacol. 47:1995;88-98.
64. Mhaouty-Kodja S., Barak L.S., Scheer A., Abuin L., Diviani D., Caron M.G., Cotecchia S. Constitutively active alpha-1b adrenergic receptor mutants display different phosphorylation and internalisation features. Mol. Pharmacol. 55:1999;339-347.
65. Möhler H., Fritschy J.M., Rudolph U. A new benzodiazepine pharmacology. J. Pharmacol Exp. Ther. 300:2002;2-8.
66. 2+ in single cells. J. Biol. Chem. 276:2001;19286-19293.
67. Neve K.A., Cox B.A., Henningsen R.A., Spanoyannis A., Neve R.L. Pivotal role for aspartate-80 in the regulation of dopamine D2 receptor affinity for drugs and inhibition of adenylyl cyclase. Mol. Pharmacol. 39:1991;733-739.
68. Neve K.A., Cumbay M.G., Thompson K.R., Yang R., Buck D.C., Watts V.J., DuRand C.J., Teeter M.M. Modelling and mutational analysis of a putative sodium-binding pocket on the dopamine D2 receptor. Mol. Pharmacol. 60:2001;373-381.
69. O'Brien J.A., Lemaire W., Chen T.-B., Chang R.S.L., Jacobson M.A., Ha S.N., Lindsley C.W., Schaffhauser H.J., Sur C., Pettibone D.J., Conn P.J., Williams D.L. Jr. A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5). Mol. Pharmacol. 64:2003;731-740.
70. Pagano A., Rüegg D., Litschig S., Stoehr N., Stierlin C., Heinrich M., Floersheim P., Prezèau L., Carroll F., Pin J.-P., Cambria A., Vranesic I., Flor P.J., Gasparini F., Kuhn R. The non-competitive antagonists MPEP and CPCCOEt interact with overlapping binding pockets in the transmembrane region of group-I glutamate receptors. J. Biol. Chem. 275:2000;35750-35758.
71. Palanche T., Ilien B., Zoffmann S., Reck M.-P., Bucher B., Edelstein S.J., Galzi J.-L. The neurokinin A receptor activates calcium and cAMP responses through distinct conformational states. J. Biol. Chem. 276:2001;34853-34861.
72. Palczewski K., Kumasaka T., Hori T., Behnke C.A., Motoshima H., Fox B.A., Le Trong I., Teller D.C., Okada T., Stenkamp R.E., Yamamoto M., Miyano M. Crystal structure of rhodopsin: a G protein-coupled receptor. Science. 289:2000;739-745.
73. Parmentier M.L., Prezeau L., Bockaert J., Pin J.P. A model for the functioning of family 3 GPCRs. Trends Pharmacol. Sci. 23:2002;268-274.
74. Parnot, C., Miserey-Lenkei, S., Bardin, S., Petrel, C., Clauser, E., 2002. Lessons from constitutively active mutants of G protein-coupled receptors. Trends Endocrinol. Metab. 13, 336-343.
75. Perez D.M., Hwa J., Gaivin R., Mathur M., Brown F., Graham R.M. Constitutive activity of a single receptor pathway: evidence for multiple activation states of a G-protein coupled receptor. Mol. Pharmacol. 49:1996;112-122.
76. 2+ sensing receptor. J. Biol. Chem. 278, 49487-49494.
77. Pierce K.L., Premont R.T., Lefkowitz R.J. Seven-transmembrane receptors. Nat. Rev. Mol. Cell. Biol. 3:2002;639-650.
78. B receptor heteromer. Neuropharmacology. 38:1999;A30-A36.
79. Rosenkilde M.M., Lubicello M., Holst B., Schwartz T.W. Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor. FEBS Lett. 439:1998;35-40.
80. Sabroe I., Peck M.J., Van Keulen B.J., Jorritsma A., Simmons G., Clapham P.R., Williams T.J., Pease J.E. A small molecule antagonist of chemokine receptors CCR1 and CCR3. Potent inhibition of eosinophil function and CCR3-mediated HIV-1 entry. J. Biol. Chem. 275:2000;25985-25992.
81. Sachpatzidis A., Benton B.K., Manfredi J.P., Wang H., Hamilton A.D., Dohlman H.G., Lolis E. Identification of allosteric peptide agonists of CXCR4. J. Biol. Chem. 278:2003;896-907.
82. 2-adrenergic receptor. J. Biol. Chem. 268:1993;4625-4636.
83. Schaffhauser H., Rowe B.A., Morales S., Chavez-Noriega L.E., Yin R., Jachec C., Rao S.P., Bain G., Pinkerton A.B., Vernier J.-M., Bristow L.J., Varney M.A., Daggett L.P. Pharmacological characterization and identification of amino acids involved in the positive modulation of metabotropic glutamate receptor subtype 2. Mol. Pharmacol. 64:2003;798-810.
84. Schetz J.A., Sibley D.R. Zinc allosterically modulates antagonist binding to cloned D1 and D2 dopamine receptors. J. Neurochem. 68:1997;1990-1997.
85. Schetz J.A., Sibley D.R. The binding-site crevice of the D4 dopamine receptor is coupled to three distinct sites of allosteric modulation. J. Pharmacol. Exp. Ther. 296:2001;359-363.
86. 2-like dopamine receptors through distinct molecular mechanisms. J. Pharmacol. Exp. Ther. 289:1999;956-964.
87. Sharpe I.A., Thomas L., Loughnan M., Motin L., Palant E., Croker D.E., Alewood D., Chen S., Graham R.M., Alewood P.F., Adams D.J., Lewis R.J. Allosteric α1-adrenoceptor antagonism by the conopeptide ρ-TIA. J. Biol. Chem. 278:2003;34451-34457.
88. Sheng M., Sala C. PDZ domains and the organization of supramolecular complexes. Annu. Rev. Neurosci. 24:2001;1-29.
89. Spalding T.A., Burstein E.S., Wells J.W., Brann M.R. Constitutive activation of the m5 muscarinic receptor by a series of mutations at the extracellular end of transmembrane 6. Biochemistry. 36:1997;10109-10116.
90. Spalding T.A., Burstein E.S., Henderson S.C., Ducote K.R., Brann M.R. Identification of a ligand-dependent switch within a muscarinic receptor. J. Biol. Chem. 273:1998;21563-21568.
91. 1 muscarinic receptor. Mol. Pharmacol. 61, 1297-1302.
92. Stockton J.M., Birdsall N.J.M., Burgen A.S.V., Hulme E.C. Modification of the binding properties of muscarinic receptors by gallamine. Mol. Pharmacol. 23:1983;551-557.
93. 2+ on the β2 adrenergic receptor. J. Biol. Chem. 278:2002a;352-356.
94. 2+. Mol. Pharmacol. 61:2002b;65-72.
95. Thomas E.A., Carson M.J., Neal M.J., Sutcliffe J.G. Unique allosteric regulation of 5-hydroxytryptamine receptor-mediated signal transduction by oleamide. Proc. Natl. Acad. Sci. U.S.A. 94:1997;14115-14119.
96. Tränkle C., Mohr K. Divergent modes of action among cationic allosteric modulators of muscarinic M2 receptors. Mol. Pharmacol. 51:1997;674-682.
97. 3+. Proc. Natl. Acad. Sci. U.S.A. 99:2002;2660-2665.
98. Tucek S., Proska J. Allosteric modulation of muscarinic acetylcholine receptors. Trends Pharmacol. Sci. 16:1995;205-212.
99. Tucek S., Musilkova J., Nedoma J., Proska J., Shelkovnikov S., Vorlicek J. Positive cooperativity in the binding of alcuronium and N-methylscopolamine to muscarinic acetylcholine receptors. Mol. Pharmacol. 38:1990;674-680.
100. B receptors by 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and its aldehyde analog CGP13501. Mol. Pharmacol. 60:2001;963-971.
101. B receptor function. J. Pharmacol. Exp. Ther. 307:2003;322-330.
102. 5 subtype selectivities of some structurally diverse allosteric ligands in N-methylscopolamine-occupied receptors. Mol. Pharmacol. 64:2003;21-31.
103. Waelbroeck M. Identification of drugs competing with d-tubocurarine for an allosteric site on cardiac muscarinic receptors. Mol. Pharmacol. 46:1994;685-692.
104. Xiao B., Tu J.C., Worley P.F. Homer: a link between neural activity and glutamate receptor function. Curr. Opin. Neurobiol. 10:2000;370-374.
105. Zahn K., Eckstein N., Tränkle C., Sadée W., Mohr K. Allosteric modulation of muscarinic receptor signalling: alcuronium-induced conversion of pilocarpine from an agonist into an antagonist. J. Pharmacol. Exp. Ther. 301:2002;720-728.
106. Zhang Z., Qiu W., Quinn S.J., Conigrave A.D., Brown E.M., Bai M. Three adjacent serines in the extracellular domains of the CaR are required for L-amino acid-mediated potentiation of receptor function. J. Biol. Chem. 277:2002;33727-33735.
107. Zhong H., Neubig R.R. Regulator of G protein signalling proteins: novel multifunctional drug targets. J. Pharmacol. Exp. Ther. 297:2001;837-845.