cAMP detection methods in HTS: selecting the best from the rest View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-02

AUTHORS

Christine Williams

ABSTRACT

Key PointsG-protein-coupled receptors (GPCRs) are one of the most important areas of research in the pharmaceutical industry.Recent years have seen an expansion in assay technologies that measure the downstream effects of activation of GPCRs. The key advantage of these functional assays is that they facilitate early and direct pharmacological characterization of compounds.This article focuses on high-throughput technologies available for the detection of changes in levels of a key intracellular signalling molecule that are modulated by GPCR activation — 3′,5′-cyclic adenosine monophosphate (cAMP).Two main types of technology for detecting changes in cAMP levels are discussed: accumulation assays and reporter-gene assays.In accumulation assays, changes in intracellular cAMP are detected by the competition between cellular cAMP and a labelled form of cAMP for binding to an anti-cAMP antibody.In reporter-gene assays, receptor-mediated changes in intracellular cAMP concentrations are detected via changes in the expression level of a particular gene (the reporter), the transcription of which is regulated by the transcription factor cAMP response-element binding protein binding to upstream cAMP response elements.Particular consideration is given to the practical and scientific implications of the methodologies, with the aim of enabling the reader to make an informed choice about their strategy for identifying GPCR modulators. More... »

PAGES

125-135

References to SciGraph publications

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  • 2002-03. Allosteric binding sites on cell-surface receptors: novel targets for drug discovery in NATURE REVIEWS DRUG DISCOVERY
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    http://scigraph.springernature.com/pub.10.1038/nrd1306

    DOI

    http://dx.doi.org/10.1038/nrd1306

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15040577


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