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Papers of the Week

Papers: 21 May 2022 - 27 May 2022

Animal Studies

2022 May 24

Proc Natl Acad Sci U S A



Serodolin, a β-arrestin-biased ligand of 5-HT receptor, attenuates pain-related behaviors.


El Khamlichi C, Reverchon F, Hervouet-Coste N, Robin E, Chopin N, Deau E, Madouri F, Guimpied C, Colas C, Menuet A, Inoue A, Bojarski AJ, Guillaumet G, Suzenet F, Reiter E, Morisset-Lopez S
Proc Natl Acad Sci U S A. 2022 May 24; 119(21):e2118847119.
PMID: 35594393.


SignificanceTransmembrane signaling through G protein-coupled receptors (GPCRs), originally described as requiring coupling to intracellular G proteins, also uses G protein-independent pathways through β-arrestin recruitment. Biased ligands, by favoring one of the multiple bioactive conformations of GPCRs, allow selective signaling through either of these pathways. Here, we identified Serodolin as the first β-arrestin-biased agonist of the serotonin 5-HT receptor. This new ligand, while acting as an inverse agonist on G signaling, selectively induces ERK activation in a β-arrestin-dependent way. Importantly, we report that Serodolin decreases pain intensity caused by thermal, mechanical, or inflammatory stimuli. Our findings suggest that targeting the 5-HTR with β-arrestin-biased ligand could be a valid alternative strategy to the use of opioids for the relief of pain.