Serodolin, a β-arrestin–biased ligand of 5-HT 7 receptor, attenuates pain-related behaviors
Résumé
Transmembrane 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 7 receptor. This new ligand, while acting as an inverse agonist on G s 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-HT 7 R with β-arrestin–biased ligand could be a valid alternative strategy to the use of opioids for the relief of pain.
Domaines
Sciences du Vivant [q-bio]| Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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