Elusive equilibrium: The challenge of interpreting receptor pharmacology using calcium assays

British Journal of Pharmacology

Volumn 161, Issue 6, 2010, Pages 1250-1265

  Charlton, Steven J ^a   Vauquelin, Georges ^b  

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^b VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

Author keywords

Agonist; Antagonist; Calcium assay; Drug discovery; Equilibrium; Hemi equilibrium; Modelling and simulation; Receptor theory

Indexed keywords

ADENOSINE TRIPHOSPHATE; CALCIUM; DYE; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN ALPHA SUBUNIT;

ALLOSTERISM; CALCIUM SIGNALING; CONCENTRATION RESPONSE; DRUG ANTAGONISM; DRUG RECEPTOR BINDING; FLUORESCENCE; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; REVIEW;

ANIMALS; CALCIUM; CALCIUM SIGNALING; HUMANS; KINETICS; PHARMACOLOGY; PROTEIN BINDING; RADIOLIGAND ASSAY; RECEPTORS, DRUG; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 77956850748     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2010.00863.x     Document Type: Review

References (61)

1. Ariens EJ (1954). Affinity and intrinsic activity in theory of compepitive inhibition. Part I. Problems and theory. Arch Int Pharmacodyn 99: 32-49.
2. Arunlakshana O, Schild HO (1959). Some quantitative uses of drug antagonists. Br J Pharmacol 14: 48-58.
3. Augustine GJ (2001). How does calcium trigger neurotransmitter release? Curr Opin Neurobiol 11: 320-326.
4. Baird GS, Zacharias DA, Tsien RY (1999). Circular permutation and receptor insertion within green fluorescent proteins. Proc Natl Acad Sci USA 96: 11241-11246.
5. Berridge MJ (1990). Calcium oscillations. J Biol Chem 265: 9583-9586.
6. Berridge MJ (2005). Calcium signalling and cell proliferation. Bioessays 17: 491-500.
7. Berridge MJ, Bootman MD, Roderick HL (2003). Calcium signalling: dynamics, homeostasis and remodeling. Nat Rev Mol Cell Biol 4: 517-529.
8. Black JW, Leff P (1983). Operational models of pharmacological agonism. Proc R Soc Lond B Biol Sci 220: 141-162.
9. 2+ indicators. Methods Enzymol 172: 164-203.
10. Bovolenta S, Foti M, Lohmer S, Corazza S (2007). Development of a Ca(2+)-activated photoprotein, Photina, and its application to high-throughput screening. J Biomol Screen 12: 694-704.
11. Brink CB, Wade SM, Neubig RR (2000). Agonist-directed trafficking of porcine alpha(2A)-adrenergic receptor signaling in Chinese hamster ovary cells: l-isoproterenol selectively activates G(s). J Pharmacol Exp Ther 294: 539-547.
12. Chambers C, Smith F, Williams C, Marcos S, Liu ZH, Hayter P et al. (2003). Measuring intracellular calcium fluxes in high throughput mode. Comb Chem High Throughput Screen 6: 355-362.
13. 50) of an enzymatic reaction. Biochem Pharmacol 22: 3099-3108.
14. Christopoulos A, Kenakin T (2002). G protein-coupled receptor allosterism and complexing. Pharmacol Rev 54: 323-374.
15. Christopoulos A, Parsons AM, Lew MJ, El-Fakahany EE (1999). The assessment of antagonist potency under conditions of transient response kinetics. Eur J Pharmacol 382: 217-227.
16. Comley J (2003). Assay interference, a limiting factor in HTS? Drug Discov World 4: 91-98.
17. Conklin BR, Farfel Z, Lustig KD, Julius D, Bourne HR (1993). Substitution of three amino acids switches receptor specificity of Gq alpha to that of Gi alpha. Nature 363: 274-276.
18. Eglen RM, Reisine T (2009). Photoproteins: important new tools in drug discovery. Assay Drug Dev Technol 6: 659-671.
19. Faehling M, Kroll J, Föhr KJ, Fellbrich G, Mayr U, Trischler G et al. (2002). Essential role of calcium in vascular endothelial growth factor A-induced signaling: mechanism of the antiangiogenic effect of carboxyamidotriazole. FASEB J 16: 1805-1807.
20. 1 receptor antagonists: the role of tight antagonist binding. Eur J Pharmacol 372: 199-206.
21. Furchgott RF (1966). The use of β-haloalkylamines in the differentiation of receptors and in the determination of dissociation constants of receptor-agonist complexes. Adv Drug Res 3: 21-55.
22. Gee KR, Brown KA, Chen WN, Bishop-Stewart J, Gray D, Johnson I (2000). Chemical and physiological characterization of fluo-4 Ca(2+)-indicator dyes. Cell Calcium 27: 97-106.
23. Greer PL, Greenberg ME (2008). From synapse to nucleus: calcium-dependent gene transcription in the control of synapse development and function. Neuron 59: 846-860.
24. Hermans E (2003). Biochemical and pharmacological control of the multiplicity of coupling at G-protein-coupled receptors. Pharmacol Ther 99: 25-44.
25. Hescheler J, Rosenthal W, Trautwein W, Schultz G (1987). The GTP-binding protein, Go, regulates neuronal calcium channels. Nature 325: 445-447.
26. Hodder P, Mull R, Cassaday J, Berry K, Strulovici B (2004). Miniaturization of intracellular calcium functional assays to 1536-well plate format using a fluorometric imaging plate reader. J Biomol Screen 9: 417-426.
27. Hofer AM, Schlue WR, Curci S, Machen TE (1995). Spatial distribution and quantitation of free luminal [Ca] within the InsP3-sensitive internal store of individual BHK-21 cells: ion dependence of InsP3-induced Ca release and reloading. FASEB J 9: 788-798.
28. Inglese J, Johnson RL, Simeonov A, Xia M, Zheng W, Austin CP et al. (2007). High-throughput screening assays for the identification of chemical probes. Nat Chem Biol 3: 466-479.
29. Jaggar JH, Porter VA, Lederer WJ, Nelson MT (2000). Calcium sparks in smooth muscle. Am J Physiol Cell Physiol 278: C235-C256.
30. Kenakin T (1995). Agonist-receptor efficacy. II. Agonist trafficking of receptor signals. Trends Pharmacol Sci 16: 232-238.
31. Kenakin T, Jenkinson S, Watson C (2006). Determining the potency and molecular mechanism of action of insurmountable antagonists. J Pharmacol Exp Ther 319: 710-723.
32. Kostenis E (2001). Is Galpha16 the optimal tool for fishing ligands of orphan G-protein-coupled receptors? Trends Pharmacol Sci 22: 560-564.
33. 1 receptor. Br J Pharmacol 151: 952-962.
34. Leff P, Dougall IG (1993). Further concerns over Cheng-Prusoff analysis. Trends Pharmacol Sci 14: 110-112.
35. 2-like receptors. Can they be classified with the available antagonists? Br J Pharmacol 88: 585-593.
36. May LT, Leach K, Sexton PM, Christopoulos A (2007). Allosteric modulation of G protein-coupled receptors. Annu Rev Pharmacol Toxicol 47: 1-51.
37. 2+ based on green fluorescent proteins and calmodulin. Nature 388: 882-887.
38. Motulsky HJ, Mahan LC (1984). The kinetics of competitive radioligand binding predicted by the law of mass action. Mol Pharmacol 25: 1-9.
39. Mulligan SJ, MacVicar BA (2005). Monitoring intracellular Ca2+ in brain slices with fluorescent indicators. In: Zamponi G (ed.). Voltage-Gated Calcium Channels. Kluwer Academic: New York, pp. 12-26.
40. Paredes RM, Etzler JC, Watts LT, Zheng W, Lechleiter J (2008). Chemical calcium indicators. Methods 46: 143-151.
41. Paton WD, Rang HP (1965). The uptake of atropine and related drugs by intestinal smooth muscle of the guinea-pig in relation to acetylcholine receptors. Proc R Soc Lond B Biol Sci 163: 1-44.
42. Pommier B, Da Nascimento S, Dumont S, Bellier B, Million E, Garbay C et al. (1999). The cholecystokininB receptor is coupled to two effector pathways through pertussis toxin-sensitive and -insensitive G proteins. J Neurochem 73: 281-288.
43. Rang HP (2006). The receptor concept: pharmacology's big idea. Br J Pharmacol 147: S9-S16.
44. Richards GR, Jack AD, Platts A, Simpson PB (2006). Measurement and analysis of calcium signaling in heterogeneous cell cultures. Methods Enzymol 414: 335-347.
45. 2+ revealed by specifically targeted recombinant aequorin. Nature 358: 325-327.
46. Rosethorne EM, Leighton-Davies JR, Beer D, Charlton SJ (2004). ATP priming of macrophage-derived chemokine responses in CHO cells expressing the CCR4 receptor. Naunyn Schmiedebergs Arch Pharmacol 370: 64-70.
47. Schroeder KS, Brad DN (1996). FLIPR: a new instrument for accurate, high throughput optical screening. J Biomol Screen 1: 75-80.
48. Selbie LA, Hill SJ (1998). G protein-coupled-receptor cross-talk: the fine-tuning of multiple receptor-signalling pathways. Trends Pharmacol Sci 19: 87-93.
49. 2+] using the Fluorometric Imaging Plate Reader (FLIPR). Methods Mol Biol 114: 125-133.
50. Sykes DA, Dowling MR, 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.
51. Takahashi A, Camacho P, Lechleiter JD, Herman B (1999). Measurement of intracellular calcium. Physiol Rev 79: 1089-1125.
52. Urban JD, Clarke WP, Von Zastrow M, Nichols DE, Kobilka B, Weinstein H et al. (2007). Functional selectivity and classical concepts of quantitative pharmacology. J Pharmacol Exp Ther 320: 1-13.
53. 1 receptors. Br J Pharmacol 126: 1057-1065.
54. 1 receptors and their non-peptide antagonists. Biochem Pharmacol 61: 277-284.
55. Vauquelin G, Van Liefde I (2006). From slow antagonist dissociation to long- lasting receptor protection. Trends Pharmacol Sci 27: 355-359.
56. Vauquelin G, Van Liefde I, Birzbier BB, Vanderheyden PML (2002a). New insights in insurmountable antagonism. Fundam Clin Pharmacol 16: 263-272.
57. Vauquelin G, Van Liefde I, Vanderheyden P (2002b). Models and methods for studying insurmountable antagonism. Trends Pharmacol Sci 23: 514-518.
58. Vauquelin G, Von Mentzer P (2007). In G-Protein Coupled Receptors: Molecular Pharmacology. Vauquelin G, Von Mentzer P (eds) John Wiley & Sons Ltd: Chichester, UK, pp. 53-64. and 185-191.
59. Wenzel-Seifert K, Seifert R (2000). Molecular analysis of beta(2)-adrenoceptor coupling to G(s)-, G(i)-, and G(q)-proteins. Mol Pharmacol 58: 954-966.
60. Werry TD, Christie MI, Dainty IA, Wilkinson GF, Willars GB (2002). Ca(2+) signalling by recombinant human CXCR2 chemokine receptors is potentiated by P2Y nucleotide receptors in HEK cells. Br J Pharmacol 135: 1199-1208.
61. Wurch T, Pauwels PJ (2001). Analytical pharmacology of G protein-coupled receptors by stoichiometric expression of the receptor and G(alpha) protein subunits. J Pharmacol Toxicol Methods 45: 3-16.