Long receptor residence time of C26 contributes to super agonist activity at the human β2 adrenoceptor

Molecular Pharmacology

Volumn 89, Issue 4, 2016, Pages 467-475

  Rosethorne, Elizabeth M ^a,c   Bradley, Michelle E ^a   Gherbi, Karolina ^a,c   Sykes, David A ^a,c   Sattikar, Afrah ^a   Wright, John D ^a   Renard, Emilie ^b   Trifilieff, Alex ^b   Fairhurst, Robin A ^b   Charlton, Steven J ^a,c  

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

^c UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

7 [2 (2 BENZYLOXYCYCLOPENTYLAMINO) 1 HYDROXYETHYL] 4 HYDROXYBENZOTHIAZOLONE; BENZOTHIAZOLE DERIVATIVE; BETA 2 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BETA ARRESTIN 2; CYCLIC AMP; EPINEPHRINE; GREEN FLUORESCENT PROTEIN; UNCLASSIFIED DRUG; PROTEIN BINDING;

AGONIST; ANIMAL TISSUE; ARTICLE; BETA ADRENERGIC STIMULATION; BINDING AFFINITY; BINDING COMPETITION; CONTROLLED STUDY; DISSOCIATION; DRUG ACTIVITY; DRUG HALF LIFE; DRUG RECEPTOR BINDING; HUMAN; HUMAN CELL; INTERNALIZATION; MALE; NONHUMAN; PHARMACOLOGICAL PARAMETERS; PRIORITY JOURNAL; PROTEIN TRANSPORT; RECEPTOR RESIDENCE TIME; SIGNAL TRANSDUCTION; TEMPERATURE; ANIMAL; CHEMISTRY; CHO CELL LINE; CRICETULUS; DOSE RESPONSE; DRUG EFFECTS; GUINEA PIG; HAMSTER; METABOLISM; ORGAN CULTURE TECHNIQUE; PHYSIOLOGY; TRACHEA; TUMOR CELL LINE;

ADRENERGIC BETA-2 RECEPTOR AGONISTS; ANIMALS; CELL LINE, TUMOR; CHO CELLS; CRICETINAE; CRICETULUS; DOSE-RESPONSE RELATIONSHIP, DRUG; GUINEA PIGS; HUMANS; MALE; ORGAN CULTURE TECHNIQUES; PROTEIN BINDING; RECEPTORS, ADRENERGIC, BETA-2; SIGNAL TRANSDUCTION; TRACHEA;

EID: 85004008278     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.115.101253     Document Type: Article

References (39)

1. Anderson GP, Lindén A, and Rabe KF (1994) Why are long-acting beta-adrenoceptor agonists long-acting? Eur Respir J 7:569-578.
2. Beattie D, Bradley M, Brearley A, Charlton SJ, Cuenoud BM, Fairhurst RA, Gedeck P, Gosling M, Janus D, and Jones D et al. (2010) A physical properties based approach for the exploration of a 4-hydroxybenzothiazolone series of β2-adrenoceptor agonists as inhaled long-acting bronchodilators. Bioorg Med Chem Lett 20:5302-5307.
3. Bennett KA, Langmead CJ, Wise A, and Milligan G (2009) Growth hormone secretagogues and growth hormone releasing peptides act as orthosteric super-agonists but not allosteric regulators for activation of the G protein Galpha(o1) by the Ghrelin receptor. Mol Pharmacol 76:802-811.
4. Black JW and Leff P (1983) Operational models of pharmacological agonism. Proc R Soc Lond B Biol Sci 220:141-162.
5. Calebiro D, Nikolaev VO, Gagliani MC, de Filippis T, Dees C, Tacchetti C, Persani L, and Lohse MJ (2009) Persistent cAMP-signals triggered by internalized G-protein-coupled receptors. PLoS Biol 7:e1000172.
6. Carter CM, Leighton-Davies JR, and Charlton SJ (2007) Miniaturized receptor binding assays: complications arising from ligand depletion. J Biomol Screen 12:255-266.
7. Cheng Y and Prusoff WH (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099-3108.
8. Childers SR, Fleming LM, Selley DE, McNutt RW, and Chang KJ (1993) BW373U86: a nonpeptidic delta-opioid agonist with novel receptor-G protein-mediated actions in rat brain membranes and neuroblastoma cells. Mol Pharmacol 44:827-834.
9. Christopoulos A and Kenakin T (2002) G protein-coupled receptor allosterism and complexing. Pharmacol Rev 54:323-374.
10. Coleman RA and Nials AT (1989) Novel and versatile superfusion system. Its use in the evaluation of some spasmogenic and spasmolytic agents using guinea-pig isolated tracheal smooth muscle. J Pharmacol Methods 21:71-86.
11. Ehlert FJ (2008) On the analysis of ligand-directed signaling at G protein-coupled receptors. Naunyn Schmiedebergs Arch Pharmacol 377:549-577.
12. Engel S, Neumann S, Kaur N, Monga V, Jain R, Northup J, and Gershengorn MC (2006) Low affinity analogs of thyrotropin-releasing hormone are super-agonists. J Biol Chem 281:13103-13109.
13. Ferrandon S, Feinstein TN, Castro M, Wang B, Bouley R, Potts JT, Gardella TJ, and Vilardaga JP (2009) Sustained cyclic AMP production by parathyroid hormone receptor endocytosis. Nat Chem Biol 5:734-742.
14. Goldman SD, Funk RS, Rajewski RA, and Krise JP (2009) Mechanisms of amine accumulation in, and egress from, lysosomes. Bioanalysis 1:1445-1459.
15. de Haën C (1976) The non-stoichiometric floating receptor model for hormone sensitive adenylyl cyclase. J Theor Biol 58:383-400.
16. Holst B, Brandt E, Bach A, Heding A, and Schwartz TW (2005) Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling. Mol Endocrinol 19:2400-2411.
17. Irannejad R, Tomshine JC, Tomshine JR, Chevalier M, Mahoney JP, Steyaert J, Rasmussen SGF, Sunahara RK, El-Samad H, and Huang B et al. (2013) Conformational biosensors reveal GPCR signalling from endosomes. Nature 495:534-538.
18. Jacobs S and Cuatrecasas P (1976) The mobile receptor hypothesis and "cooperativity" of hormone binding. Application to insulin. Biochim Biophys Acta (BBA) -. Biomembranes 433:482-495.
19. Kenakin T and Christopoulos A (2013) Signalling bias in new drug discovery: detection, quantification and therapeutic impact. Nat Rev Drug Discov 12:205-216.
20. Leach K, Sexton PM, and Christopoulos A (2007) Allosteric GPCR modulators: taking advantage of permissive receptor pharmacology. Trends Pharmacol Sci 28:382-389.
21. Motulsky HJ and Mahan LC (1984) The kinetics of competitive radioligand binding predicted by the law of mass action. Mol Pharmacol 25:1-9.
22. Mullershausen F, Zecri F, Cetin C, Billich A, Guerini D, and Seuwen K (2009) Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. Nat Chem Biol 5:428-434.
23. Nygaard R, Zou Y, Dror RO, Mildorf TJ, Arlow DH, Manglik A, Pan AC, Liu CW, Fung JJ, and Bokoch MP et al. (2013) The dynamic process of β(2)-adrenergic receptor activation. Cell 152:532-542.
24. Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, and Calinski D et al. (2011) Crystal structure of the β2 adrenergic receptor-Gs protein complex. Nature 477:549-555.
25. Roberts DJ, Lin H, and Strange PG (2004) Investigation of the mechanism of agonist and inverse agonist action at D2 dopamine receptors. Biochem Pharmacol 67:1657-1665.
26. Rosethorne EM, Bradley ME, Kent TC, and Charlton SJ (2015) Functional desensitization of the β 2 adrenoceptor is not dependent on agonist efficacy. Pharmacol Res Perspect 3:e00101.
27. Rosethorne EM, Turner RJ, Fairhurst RA, and Charlton SJ (2010) Efficacy is a contributing factor to the clinical onset of bronchodilation of inhaled beta(2)-adrenoceptor agonists. Naunyn Schmiedebergs Arch Pharmacol 382:255-263.
28. Schneider EH, Schnell D, Papa D, and Seifert R (2009) High constitutive activity and a G-protein-independent high-affinity state of the human histamine H(4)-receptor. Biochemistry 48:1424-1438.
29. Schrage R, Seemann WK, Klöckner J, Dallanoce C, Racké K, Kostenis E, De Amici M, Holzgrabe U, and Mohr K (2013) Agonists with supraphysiological efficacy at the muscarinic M2 ACh receptor. Br J Pharmacol 169:357-370.
30. Strange PG (2008) Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors. Br J Pharmacol 153:1353-1363.
31. Sykes DA and Charlton SJ (2012) Slow receptor dissociation is not a key factor in the duration of action of inhaled long-acting β2-adrenoceptor agonists. Br J Pharmacol 165:2672-2683.
32. Sykes DA, Dowling MR, and Charlton SJ (2009) Exploring the mechanism of agonist efficacy: a relationship between efficacy and agonist dissociation rate at the muscarinic M3 receptor. Mol Pharmacol 76:543-551.
33. Sykes DA, Dowling MR, and Charlton SJ (2010) Measuring receptor target coverage: a radioligand competition binding protocol for assessing the association and dissociation rates of unlabeled compounds, in Current Protocols in Pharmacology 50:9.14:9.14.1-9.14.30.
34. Sykes DA, Riddy DM, Stamp C, Bradley ME, McGuiness N, Sattikar A, Guerini D, Rodrigues I, Glaenzel A, and Dowling MR et al. (2014) Investigating the molecular mechanisms through which FTY720-P causes persistent S1P1 receptor internalization. Br J Pharmacol 171:4797-4807.
35. Tetko IV, Gasteiger J, Todeschini R, Mauri A, Livingstone D, Ertl P, Palyulin VA, Radchenko EV, Zefirov NS, and Makarenko AS et al. (2005) Virtual Computational Chemistry Laboratory - Design and Description. J Comput Aid Mol Des 19:453-463.
36. Vanhauwe JFM, Fraeyman N, Francken BJB, Luyten WHML, and Leysen JE (1999) Comparison of the ligand binding and signaling properties of human dopamine D (2) and D(3) receptors in Chinese hamster ovary cells. J Pharmacol Exp Ther 290:908-916.
37. Waelbroeck M, Boufrahi L, and Swillens S (1997) Seven helix receptors are enzymes catalysing G protein activation. What is the agonist Kact? J Theor Biol 187:15-37.
38. Weiss JM, Morgan PH, Lutz MW, and Kenakin TP (1996) The cubic ternary complex receptor-occupancy model. III. resurrecting efficacy. J Theor Biol 181:381-397.
39. Yan F, Mosier PD, Westkaemper RB, and Roth BL (2008) Galpha-subunits differentially alter the conformation and agonist affinity of kappa-opioid receptors. Biochemistry 47:1567-1578.