Oxyntomodulin differentially affects glucagon-like peptide-1 receptor beta-arrestin recruitment and signaling through Galpha(s)
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Oxyntomodulin differentially affects glucagon-like peptide-1 receptor beta-arrestin recruitment and signaling through Galpha(s). / Jorgensen, Rasmus; Kubale, Valentina; Vrecl, Milka; Schwartz, Thue W; Elling, Christian E.
In: Journal of Pharmacology and Experimental Therapeutics, Vol. 322, No. 1, 2007, p. 148-54.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Oxyntomodulin differentially affects glucagon-like peptide-1 receptor beta-arrestin recruitment and signaling through Galpha(s)
AU - Jorgensen, Rasmus
AU - Kubale, Valentina
AU - Vrecl, Milka
AU - Schwartz, Thue W
AU - Elling, Christian E
N1 - Keywords: Animals; Arrestins; COS Cells; Cercopithecus aethiops; Cyclic AMP; G-Protein-Coupled Receptor Kinase 2; G-Protein-Coupled Receptor Kinase 5; GTP-Binding Protein alpha Subunits, Gs; Glucagon; Glucagon-Like Peptide 1; Humans; Luminescent Measurements; Oxyntomodulin; Protein-Serine-Threonine Kinases; Receptors, Glucagon; Signal Transduction; beta-Adrenergic Receptor Kinases
PY - 2007
Y1 - 2007
N2 - 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 transfer assays to measure agonist-induced recruitment of betaarrestins 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 betaarrestins and GRK2 to the GLP-1 receptor. We suggest that oxyntomodulin and glucagon are biased ligands on the GLP-1 receptor.
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 transfer assays to measure agonist-induced recruitment of betaarrestins 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 betaarrestins and GRK2 to the GLP-1 receptor. We suggest that oxyntomodulin and glucagon are biased ligands on the GLP-1 receptor.
U2 - 10.1124/jpet.107.120006
DO - 10.1124/jpet.107.120006
M3 - Journal article
C2 - 17395766
VL - 322
SP - 148
EP - 154
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 1
ER -
ID: 21666285