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Research Article

An optical dynamic mass redistribution assay reveals biased signaling of dualsteric GPCR activators

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Pages 140-145 | Received 15 Jan 2009, Accepted 11 Mar 2009, Published online: 08 Jul 2009

References

  • Kenakin T. Collateral efficacy in drug discovery: Taking advantage of the good (allosteric) nature of 7TM receptors. Trends Pharmacol Sci 2007;28:407–15.
  • Seifert R, Dove S. Functional selectivity of GPCR ligand stereoisomers: New pharmacological opportunities. Mol Pharmacol 2009;75:13–8.
  • Violin JD, Lefkowitz J. ß-arrestin-biased ligands at seven-transmembrane receptors. Trends Pharmacol Sci 2007;28:416–22.
  • Antony J, Kellershohn K, Mohr-Andrä; M, Kebig A, Prilla S, Muth M, Heller E, Disingrini T, Dallanoce C, Bertoni S, Schrobang J, Tränkle C, Kostenis E, Christopoulos A, Höltje HD, Barocelli E, De Amici M, Holzgrabe U, Mohr K. Dualsteric GPCR targeting: a novel route to binding and signaling pathway selectivity. FASEB J 2009; 23:442–50.
  • Birdsall NJ, Lazareno S. Allosterism at muscarinic receptors: ligands and mechanisms. Mini Rev Med Chem 2005;5:523–43.
  • Disingrini T, Muth M, Dallanoce C, Barocelli E, Bertoni S, Kellershohn K, Mohr K, De Amici M, Holzgrabe U. Design, synthesis, and action of oxotremorine-related hybrid-type allosteric modulators of muscarinic acetylcholine receptors. J Med Chem 2006;49:366–72.
  • Fang Y, Ferrie AM, Fontaine NH, Mauro J, Balakrishnan J. Resonant waveguide grating biosensor for living cell sensing. Biophys J 2006;91:1925–40.
  • Fang Y, Li G, Ferrie AM. Non-invasive optical biosensor for assaying endogenous G protein-coupled receptors in adherent cells. J Pharmacol Toxicol Methods 2007;55:314–22.
  • Dallanoce C, Conti P, De Amici M, De Micheli C, Barocelli E, Chiavarini M, Ballabeni V, Bertoni S, Impicciatore M. Synthesis and functional characterization of novel derivatives related to oxotremorine and oxotremorine-M. Bioorg Med Chem 1999;7:1539–47.
  • Fang Y. Non-invasive optical biosensor for probing cell signaling. Sensors 2007;7:2316–29.
  • Lee PH, Gao A, van Staden C, Ly J, Salon J, Xu A, Fang Y, Verkleeren R. Evaluation of dynamic mass redistribution technology for pharmacological studies of recombinant and endogenously expressed GPCRs. Assay Drug Dev Technol 2008;6:83–94.
  • Zahn K, Eckstein N, Tränkle C, Sadée 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;301:720–28.
  • Jäger D, Schmalenbach C, Prilla S, Schrobang J, Kebig A, Sennwitz M, Heller E, Tränkle C, Holzgrabe U, Höltje HD, Mohr K. Allosteric small molecules unveil a role of an extracellular E2/transmembrane helix 7 junction for G protein-coupled receptor activation. J Biol Chem 2007;282:34968–76.
  • Wess J, Eglen RM, Gautam D. Muscarinic acetylcholine receptors: Mutant mice provide new insights for drug development. Nat Rev Drug Discov 2007;6:721–33.
  • Ellis J, Huyler J, Brann MR. Allosteric regulation of cloned m1-m5 muscarinic receptor subtypes. Biochem Pharmacol 1991;42:1927–32.
  • Jakubík J, Bacáková; L, El-Fakahany EE, Tuček S. Subtype-selectivity of the positive allosteric action of alcuronium at cloned M1-M5 muscarinic acetylcholine receptors. J Pharmacol Exp Ther 1995;274:1077–83.
  • Buller S, Zlotos DP, 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 2002;61:160–8.
  • Huang XP, Prilla S, Mohr K, Ellis J. Critical amino acid residues of the common allosteric site on the M2 muscarinic acetylcholine receptor: more similarities than differences between the structurally divergent agents gallamine and bis(ammonio)alkane-type hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)ammonium]dibromide. Mol Pharmacol 2005;68:769–78.
  • Kaslow HR, Lim LK, Moss J, Lesikar DD. Structure-activity analysis of the activation of pertussis toxin. Biochemistry 1987;26:123–7.
  • Mistry R, Dowling MR, Challiss RA. An investigation of whether agonist-selective receptor conformations occur with respect to M2 and M4 muscarinic acetylcholine receptor signalling via Gi/o and Gs proteins. Br J Pharmacol 2005;144:566–75.
  • Griffin MT, Figueroa KW, Liller S, Ehlert FJ. Estimation of agonist activity at G protein-coupled receptors: analysis of M2 muscarinic receptor signaling through Gi/o, Gs, and G15. J Pharmacol Exp Ther 2007;321:1193–207.
  • Michal P, El-Fakahany EE, Dolezal V. Muscarinic M2 receptors directly activate Gq/11 and Gs G-proteins. J Pharmacol Exp Ther 2001;320:607–14.
  • Mohr K, Tränkle C, Holzgrabe U. Structure/activity relationships of M2 muscarinic allosteric modulators. Receptors Channels 2003;9:229–40.
  • Voigtländer U, Jöhren K, Mohr M, Raasch A, Tränkle C, Buller S, Ellis J, Höltje HD, Mohr K. Allosteric site on muscarinic acetylcholine receptors: Identification of two amino acids in the muscarinic M2 receptor that account entirely for the M2/M5 subtype selectivities of some structurally diverse allosteric ligands in N-methylscopolamine-occupied receptors. Mol Pharmacol 2003;64:21–31.
  • Prilla S, Schrobang J, Ellis J, Höltje HD, Mohr K. Allosteric interactions with muscarinic acetylcholine receptors: Complex role of the conserved tryptophan M2422Trp in a critical cluster of amino acids for baseline affinity, subtype selectivity, and cooperativity. Mol Pharmacol 2006;70:181–93.

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