The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
The role of kinetic context in apparent biased agonism at GPCRs
Abstract
Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that ‘kinetic context’, as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D 2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism.
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Self-citationOperational models of pharmacological agonism
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Research works printed but not linked: 1
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How Ligands Illuminate GPCR Molecular Pharmacology
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Self-citationCommunity guidelines for GPCR ligand bias: IUPHAR review 32
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Self-citationAllostery and biased agonism at class B G protein-coupled receptors
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Metadata
- Authors
- Klein Herenbrink, C., Sykes, D. A., Donthamsetti, P., Canals, M., Coudrat, T., Shonberg, J., Scammells, P. J., Capuano, B., Sexton, P. M., Charlton, S. J., Javitch, J. A., Christopoulos, A., & Lane, J. R.
- Venue
- Nature Communications
- Published
- 2016-02-24
- Volume
- 7
- Issue
- 1
- ISSN
- 2041-1723
- Cited by
- 328
- References
- 65
- Language
- en
- Licence
- creativecommons.org/licenses/by/4.0 (tdm)
- creativecommons.org/licenses/by/4.0 (vor)
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- Klein Herenbrink, C., Sykes, D. A., Donthamsetti, P., Canals, M., Coudrat, T., Shonberg, J., Scammells, P. J., Capuano, B., Sexton, P. M., Charlton, S. J., Javitch, J. A., Christopoulos, A., & Lane, J. R. (2016). The role of kinetic context in apparent biased agonism at GPCRs. Nature Communications. https://doi.org/10.1038/ncomms10842
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