Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-22T16:29:27.220Z Has data issue: false hasContentIssue false

12 - Assays to read GPCR modulation and signaling

from PART III - GPCR SIGNALING FEATURES

Published online by Cambridge University Press:  05 June 2012

By
Ralf Heilker  and
Michael Wolff
Edited by
Sandra Siehler  and
Graeme Milligan
Ralf Heilker
Affiliation:
Boehringer Ingelheim Pharma GmbH & Co. KG
Michael Wolff
Affiliation:
Boehringer Ingelheim Pharma GmbH & Co. KG
Sandra Siehler
Affiliation:
Novartis Institute for Biomedical Research
Graeme Milligan
Affiliation:
University of Glasgow
Get access

Summary

A summary is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.
Image of the first page of this content. For PDF version, please use the ‘Save PDF’ preceeding this image.'
Type
Chapter
Information
G Protein-Coupled Receptors
Structure, Signaling, and Physiology
 , pp. 231 - 246
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Jacoby, E., Bouhelal, R., Gerspacher, M., and Seuwen, K. (2006). The 7 TM G-protein-coupled receptor target family. ChemMedChem. 1, 761–782.CrossRefGoogle ScholarPubMed
Gierschik, P., Sidiropoulos, D., Steisslinger, M., and Jakobs, K.H. (1989). Na+ regulation of formyl peptide receptor-mediated signal transduction in HL 60 cells. Evidence that the cation prevents activation of the G-protein by unoccupied receptors. Eur. J. Pharmacol. 172, 481–492.CrossRefGoogle ScholarPubMed
Costa, T. and Herz, A. (1989). Antagonists with negative intrinsic activity at delta opioid receptors coupled to GTP-binding proteins. Proc. Natl. Acad. Sci. U. S. A 86, 7321–7325.CrossRefGoogle ScholarPubMed
Greasley, P.J. and Clapham, J.C. (2006). Inverse agonism or neutral antagonism at G-protein coupled receptors: a medicinal chemistry challenge worth pursuing?Eur. J. Pharmacol. 553, 1–9.CrossRefGoogle ScholarPubMed
Fox, G.B., Pan, J.B., Esbenshade, T.A., Bitner, R.S., Nikkel, A.L., Miller, T., Kang, C.H., Bennani, Y.L., Black, L.A., Faghih, R., Hancock, A.A., and Decker, M.W. (2002). Differential in vivo effects of H3 receptor ligands in a new mouse dipsogenia model. Pharmacol. Biochem. Behav. 72, 741–750.CrossRefGoogle Scholar
Harvey, J.A., Welsh, S.E., Hood, H., and Romano, A.G. (1999). Effect of 5-HT2 receptor antagonists on a cranial nerve reflex in the rabbit: evidence for inverse agonism. Psychopharmacology (Berl) 141, 162–168.CrossRefGoogle ScholarPubMed
Engelhardt, S., Grimmer, Y., Fan, G.H., and Lohse, M.J. (2001). Constitutive activity of the human beta(1)-adrenergic receptor in beta(1)-receptor transgenic mice. Mol. Pharmacol. 60, 712–717.Google ScholarPubMed
Drake, M.T., Violin, J.D., Whalen, E.J., Wisler, J.W., Shenoy, S.K., and Lefkowitz, R.J. (2008). {beta}-Arrestin-biased Agonism at the {beta}2-Adrenergic Receptor. J. Biol. Chem. 283, 5669–5676.CrossRefGoogle Scholar
Sorg, G., Schubert, H.D., Buttner, F.H., Valler, M.J., and Heilker, R. (2002b). Comparison of photomultiplier tube- and charge coupled device-based scintillation counting. Life Science News 11, 1–3.Google Scholar
Ramm, P. (1999). Imaging systems in assay screening. Drug Discov. Today 4, 401–410.CrossRefGoogle ScholarPubMed
Milligan, G. (2003). Principles: extending the utility of [35S]GTP gamma S binding assays. Trends Pharmacol. Sci. 24, 87–90.CrossRefGoogle Scholar
Gonzalez-Maeso, J., Ang, R.L., Yuen, T., Chan, P., Weisstaub, N.V., Lopez-Gimenez, J.F., Zhou, M., Okawa, Y., Callado, L.F., Milligan, G., Gingrich, J.A., Filizola, M., Meana, J.J., and Sealfon, S.C. (2008). Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452, 93–97.CrossRefGoogle ScholarPubMed
Osmond, R.I., Sheehan, A., Borowicz, R., Barnett, E., Harvey, G., Turner, C., Brown, A., Crouch, M.F., and Dyer, A.R. (2005). GPCR screening via ERK 1/2: a novel platform for screening G protein-coupled receptors. J. Biomol. Screen. 10, 730–737.CrossRefGoogle ScholarPubMed
Sullivan, E., Tucker, E.M., and Dale, I.L. (1999). Measurement of [Ca2+] using the Fluorometric Imaging Plate Reader (FLIPR). Methods Mol. Biol. 114, 125–133.Google Scholar
Alouani, S. (2000). Scintillation proximity binding assay. Methods Mol. Biol. 138, 135–141.Google ScholarPubMed
Banks, P. and Harvey, M. (2002). Considerations for using fluorescence polarization in the screening of g protein-coupled receptors. J. Biomol. Screen. 7, 111–117.CrossRefGoogle ScholarPubMed
Wolff, M., Kauschke, S.G., Schmidt, S., and Heilker, R. (2008). Activation and Translocation of Glucokinase in Rat Primary Hepatocytes Monitored by High Content Image Analysis. J. Biomol. Screen. 13, 837–46.CrossRefGoogle ScholarPubMed
Parmentier, M. and Detheux, M. (2006). Deorphanization of G-protein-coupled receptors. Ernst Schering Found. Symp. Proc. 2, 163–186.Google Scholar
Sorg, G., Schubert, H.D., Buttner, F.H., and Heilker, R. (2002a). Automated high throughput screening for serine kinase inhibitors using a LEADseeker scintillation proximity assay in the 1536-well format. J. Biomol. Screen. 7, 11–19.CrossRefGoogle ScholarPubMed
Sorg, G. and Heilker, R. (2002). Automated high-throughput screening. European Pharmaceutical Review 3, 25–35.Google Scholar
Jessop, R.A. (1998). Imaging proximity assays. Proc. SPIE 3259, 228–233.CrossRefGoogle Scholar
Harris, A., Cox, S., Burns, D., and Norey, C. (2003). Miniaturization of fluorescence polarization receptor-binding assays using CyDye-labeled ligands. J. Biomol. Screen. 8, 410–420.CrossRefGoogle Scholar
Haupts, U., Rudiger, M., and Pope, A.J. (2000). Macroscopic versus microscopic fluorescence techniques in (ultra)-high-throughput screening. Drug Discov. Today HTS Suppl 1, 3–9.CrossRefGoogle Scholar
Auer, M., Moore, K.J., Meyer-Almes, F.J., Guenther, R., Pope, A.J., and Stoeckli, K. (1998). Fluorescence correlation spectroscopy: lead discovery by miniaturized HTS. Drug Discov. Today 3, 457–465.Google Scholar
Zemanova, L., Schenk, A., Valler, M.J., Nienhaus, G.U., and Heilker, R. (2003). Confocal optics microscopy for biochemical and cellular high-throughput screening. Drug Discov. Today 8, 1085–1093.Google ScholarPubMed
Siehler, S. (2008). Cell-based assays in GPCR drug discovery. Biotechnol. J. 3, 471–483.CrossRefGoogle ScholarPubMed
Heilker, R., Zemanova, L., Valler, M.J., and Nienhaus, G.U. (2005). Confocal fluorescence microscopy for high-throughput screening of G-protein coupled receptors. Current Medicinal Chemistry 12, 2551–2559.CrossRefGoogle ScholarPubMed
Shenoy, S.K., Drake, M.T., Nelson, C.D., Houtz, D.A., Xiao, K., Madabushi, S., Reiter, E., Premont, R.T., Lichtarge, O., and Lefkowitz, R.J. (2006). beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor. J. Biol. Chem. 281, 1261–1273.CrossRefGoogle Scholar
Cabrera-Vera, T.M., Vanhauwe, J., Thomas, T.O., Medkova, M., Preininger, A., Mazzoni, M.R., and Hamm, H.E. (2003). Insights into G protein structure, function, and regulation. Endocr. Rev. 24, 765–781.CrossRefGoogle ScholarPubMed
Oakley, R.H., Laporte, S.A., Holt, J.A., Barak, L.S., and Caron, M.G. (2001). Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor endocytosis*. J. Biol. Chem. 276, 19452–19460.CrossRefGoogle Scholar
Meyer, B.H., Freuler, F., Guerini, D., and Siehler, S. (2008). Reversible translocation of p115-RhoGEF by G(12/13)-coupled receptors. J. Cell Biochem. 104, 1660–1670.CrossRefGoogle Scholar
Delapp, N.W. (2004). The antibody-capture [(35)S]GTPgammaS scintillation proximity assay: a powerful emerging technique for analysis of GPCR pharmacology. Trends Pharmacol. Sci. 25, 400–401.CrossRefGoogle ScholarPubMed
Kostenis, E., Waelbroeck, M., and Milligan, G. (2005). Techniques: Promiscuous Galpha proteins in basic research and drug discovery. Trends Pharmacol. Sci. 26, 595–602.CrossRefGoogle ScholarPubMed
Strange, P.G. (2008). Signaling mechanisms of GPCR ligands. Curr. Opin. Drug Discov. Devel. 11, 196–202.Google ScholarPubMed
Dupriez, V.J., Maes, K., Poul, E., Burgeon, E., and Detheux, M. (2002). Aequorin-based functional assays for G-protein-coupled receptors, ion channels, and tyrosine kinase receptors. Receptors. Channels 8, 319–330.CrossRefGoogle ScholarPubMed
Gabriel, D., Vernier, M., Pfeifer, M.J., Dasen, B., Tenaillon, L., and Bouhelal, R. (2003). High throughput screening technologies for direct cyclic AMP measurement. Assay Drug Dev. Technol. 1, 291–303.CrossRefGoogle ScholarPubMed
Hill, S.J., Baker, J.G., and Rees, S. (2001). Reporter-gene systems for the study of G-protein-coupled receptors. Curr. Opin. Pharmacol. 1, 526–532.CrossRefGoogle Scholar
Berridge, M.J. (1993). Inositol trisphosphate and calcium signalling. Nature 361, 315–325.CrossRefGoogle ScholarPubMed
Offermanns, S. (2003). G-proteins as transducers in transmembrane signalling. Prog. Biophys. Mol. Biol. 83, 101–130.CrossRefGoogle ScholarPubMed
Wolff, M., Kredel, S., Haasen, D., Wiedenmann, J., Nienhaus, G.U., Kistler, B., Oswald, F., and Heilker, R. (2010). High content screening of CXCR2-dependent signalling pathways. Comb. Chem. High Throughput Screen. 13, 3–15.CrossRefGoogle ScholarPubMed
Lefkowitz, R.J. (1998). G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization. J. Biol. Chem. 273, 18677–18680.CrossRefGoogle ScholarPubMed
Richman, J.G., Kanemitsu-Parks, M., Gaidarov, I., Cameron, J.S., Griffin, P., Zheng, H., Guerra, N.C., Cham, L., iejewski-Lenoir, D., Behan, D.P., Boatman, D., Chen, R., Skinner, P., Ornelas, P., Waters, M.G., Wright, S.D., Semple, G., and Connolly, D.T. (2007). Nicotinic acid receptor agonists differentially activate downstream effectors. J. Biol. Chem. 282, 18028–18036.CrossRefGoogle ScholarPubMed
Eglen, R.M. (2005). Functional G protein-coupled receptor assays for primary and secondary screening. Comb. Chem. High Throughput Screen. 8, 311–318.CrossRefGoogle ScholarPubMed
Bullen, A. (2008). Microscopic imaging techniques for drug discovery. Nat. Rev. Drug Discov. 7, 54–67.CrossRefGoogle ScholarPubMed
Hoffman, A.F. and Garippa, R.J. (2007). A pharmaceutical company user's perspective on the potential of high content screening in drug discovery. Methods Mol. Biol. 356, 19–31.Google ScholarPubMed
Giuliano, K.A., Johnston, P.A., Gough, A., and Taylor, D.L. (2006). Systems cell biology based on high-content screening. Methods Enzymol. 414, 601–619.CrossRefGoogle ScholarPubMed
Carpenter, A.E. (2007). Image-based chemical screening. Nat. Chem. Biol. 3, 461–465.CrossRefGoogle ScholarPubMed
Krausz, E. (2007). High-content siRNA screening. Mol. Biosyst. 3, 232–240.CrossRefGoogle ScholarPubMed
Wolff, M., Haasen, D., Merk, S., Kroner, M., Maier, U., Bordel, S., Wiedenmann, J., Nienhaus, G.U., Valler, M.J., and Heilker, R. (2006). Automated High Content Screening for phosphoinositide 3 kinase inhibition using an AKT1 redistribution assay. Comb. Chem. High Throughput Screen. 9, 339–350.CrossRefGoogle ScholarPubMed
Wigglesworth, M.J., Wolfe, L.A., and Wise, A. (2006). Orphan seven transmembrane receptor screening. Ernst Schering Found. Symp. Proc. 105–143.Google Scholar
Heilker, R., Wolff, M., Tautermann, C.S., and Bieler, M. (2009). G-protein-coupled receptor-focused drug discovery using a target class platform approach. Drug Discov. Today 14, 231–40.CrossRefGoogle ScholarPubMed
Heilker, R. (2006). High Content Screening to monitor G-protein coupled receptor internalisation. Ernst Schering Foundation Symposium Proceedings 2, 229–248.Google Scholar
Haasen, D., Schnapp, A., Valler, M.J., and Heilker, R. (2006). G protein-coupled receptor internalization assays in the high-content screening format. Methods Enzymol. 414, 121–139.CrossRefGoogle ScholarPubMed
Haasen, D., Merk, S., Seither, P., Martyres, D., Hobbie, S., and Heilker, R. (2008). Pharmacological profiling of chemokine receptor-directed compounds using high-content screening. J. Biomol. Screen. 13, 40–53.CrossRefGoogle ScholarPubMed
Ferguson, S.S. (2001). Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol. Rev. 53, 1–24.Google Scholar
Milligan, G. (2004). G protein-coupled receptor dimerization: function and ligand pharmacology. Mol. Pharmacol. 2004. Jul.;66. (1):1–7. 66, 1–7.CrossRefGoogle ScholarPubMed
Oakley, R.H., Hudson, C.C., Cruickshank, R.D., Meyers, D.M., Payne, R.E., Rhem, S.M., and Loomis, C.R. (2002). The cellular distribution of fluorescently labeled arrestins provides a robust, sensitive, and universal assay for screening of G protein-coupled receptors. Assay Drug Dev. Technol. 1, 21–30.CrossRefGoogle ScholarPubMed
Kredel, S., Wolff, M., Wiedenmann, J., Moepps, B., Nienhaus, G.U., Gierschik, P., Kistler, B., and Heilker, R. (2009). CXCR2 inverse agonism detected by arrestin redistribution. J. Biomol. Screen. 14, 1076–91.CrossRefGoogle ScholarPubMed
Feliciello, A., Gottesman, M.E., and Avvedimento, E.V. (2001). The biological functions of A-kinase anchor proteins. J. Mol. Biol. 308, 99–114.CrossRefGoogle ScholarPubMed
Lefkowitz, R.J. and Shenoy, S.K. (2005). Transduction of receptor signals by beta-arrestins. Science 308, 512–517.CrossRefGoogle ScholarPubMed
Fang, Y., Frutos, A.G., and Verklereen, R. (2008). Label-free cell-based assays for GPCR screening. Comb. Chem. High Throughput Screen. 11, 357–369.CrossRefGoogle Scholar
Zemanova, L., Schenk, A., Valler, M.J., Nienhaus, G.U., and Heilker, R. (2005). High-throughput screening of interactions between G protein-coupled receptors and ligands using confocal optics microscopy. Methods Mol. Biol. 305, 365–384.Google ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×