In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-06-10)
Abstract:
The signalling of the D 2 receptor (D 2 R), a G protein-coupled receptor (GPCR), is a complex process consisting of various components. For the screening of D 2 R ligands, methods quantifying distinct second messengers such as cAMP or the interaction of the receptor with β-arrestin, are commonly employed. In contrast, a label-free biosensor technology like dynamic mass redistribution (DMR), where it is mostly unknown how the individual signalling pathways contribute to the DMR signal, provides a holistic readout of the complex cellular response. In this study, we report the successful application of the DMR technology to CHO-K1 cells stably expressing the human dopamine D 2long receptor. In real-time kinetic experiments, studies of D 2 R reference compounds yielded results for agonists and antagonists that were consistent with those obtained by conventional methods and also allowed a discrimination between partial and full agonists. Furthermore, investigations on the signalling pathway in CHO-K1 hD 2long R cells identified the Gα i/o protein as the main proximal trigger of the observed DMR response. The present study has shown that the DMR technology is a valuable method for the characterisation of putative new ligands and, due to its label-free nature, suggests its use for deorphanisation studies of GPCRs.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-022-14311-w
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2615211-3
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