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Differential functional selectivity and downstream signaling bias of ghrelin receptor antagonists and inverse agonists.

FASEB J.. 2018-07; 
RamirezValerie T,van OeffelenWesley E P A,Torres-FuentesCristina,ChruścickaBarbara,DruelleClementine,GolubevaAnna V,van de WouwMarcel,DinanTimothy G,CryanJohn F,SchellekensHarr
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… Proteins were separated on 4-20% polyacrylamide gel (M00655; GenScript, Piscataway, NJ, USA)…

摘要

The ghrelin receptor [growth hormone secretagogue receptor (GHSR)-1a] represents a promising pharmacologic target for the treatment of metabolic disorders, including obesity and cachexia, via central appetite modulation. The GHSR-1a has a complex pharmacology, highlighted by G-protein-dependent and -independent downstream signaling pathways and high basal constitutive activity. The functional selectivity and signaling bias of many GHSR-1a-specific ligands has not been fully characterized. In this study, we investigated the pharmacologic properties of ghrelin, MK-0677, L692,585, and [d-Lys3]-growth hormone-releasing peptide-6 (Dlys), JMV2959, and [d-Arg(1),d-Phe(5),d-Trp(7, 9),Leu(11)... More

关键词

GHSR-1a,GPCR,probe of depend