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Is the neuropeptide PEN a ligand of GPR83?

Giesecke, Y.; Asimi, V.; Stulberg, V.; Kleinau, G.; Scheerer, P.; Koksch, B.; Groetzinger, C.

2023-09-03 pharmacology and toxicology
10.1101/2023.08.31.555736 bioRxiv
Show abstract

G protein-coupled receptor 83 (GPR83) is a class A G protein-coupled receptor with predominant expression in the cerebellum and proposed function in the regulation of food intake and in anxiety-like behavior. The neuropeptide PEN has been suggested as a specific GPR83 ligand. However, conflicting reports exist about whether PEN is indeed able to bind and activate GPR83. This study was initiated to evaluate PEN as a potential ligand of GPR83. Employing several second-messenger and other GPCR activation assays as well as a radioligand binding assay, and using multiple GPR83 plasmids and PEN peptides from different sources, no experimental evidence was found to support a role of PEN as a GPR83 ligand.

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