RT Journal Article
SR Electronic
T1 Oxyntomodulin Differentially Affects Glucagon-Like Peptide-1 Receptor β-Arrestin Recruitment and Signaling through Gα
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 148
OP 154
DO 10.1124/jpet.107.120006
VO 322
IS 1
A1 Rasmus Jorgensen
A1 Valentina Kubale
A1 Milka Vrecl
A1 Thue W. Schwartz
A1 Christian E. Elling
YR 2007
UL http://jpet.aspetjournals.org/content/322/1/148.abstract
AB The glucagon-like peptide (GLP)-1 receptor is a promising target for the treatment of type 2 diabetes and obesity, and there is great interest in characterizing the pharmacology of the GLP-1 receptor and its ligands. In the present report, we have applied bioluminescence resonance energy transfer2 assays to measure agonist-induced recruitment of βarrestins and G-protein-coupled receptor kinase (GRK) 2 to the GLP-1 receptor in addition to traditional measurements of second messenger generation. The peptide hormone oxyntomodulin is described in the literature as a full agonist on the glucagon and GLP-1 receptors. Surprisingly, despite being full agonists in GLP-1 receptor-mediated cAMP accumulation, oxyntomodulin and glucagon were observed to be partial agonists in recruiting βarrestins and GRK2 to the GLP-1 receptor. We suggest that oxyntomodulin and glucagon are biased ligands on the GLP-1 receptor. The American Society for Pharmacology and Experimental Therapeutics