Characterization Of The Agonists Of Neuromedin U 2 Receptor

Neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. The agonists of NMU2R could be developed into effective therapeutic drug for the treatment of obesity. However, the molecular mechanism underlying the actions of NMU2R has not been clearly defined. In the present study, we have analyzed the activity of NMU2R agonists in human NMU2R cell line and examined the involvement of peptides in the regulation of NMU2R effects.1. The establishment of NMU2R cell lineHuman NMU2R cDNA was cloned using PCR method and the sequence of the cDNA clone was confirmed. The PCR product was subcloned into mammalian expression vector pcDNA3.1(+). HEK-293 cells were co-transfected with the reporter gene construct and human NMU2R cDNA. Forskolin and NMU were applied to the cell line to evaluate the cell-based functional assay. The luciferase assay results showed that the receptor in the cell line could be activated in a dose response manner.2. The activity analysis of NMU2R agonistsSeveral structural related natural product compounds have been identified as specific agonists for NMU2R. The compounds belong to flavonoid glycosides. A number of analogs were synthesized for structure-activity analysis (SAR). In vitro pharmacological analysis indicated the synthetic compounds Mml-7 and Zsg-3 had higher affinity to the human NMU2R than the natural product compounds. The EC50 values for the receptor were 14.012uM and 16.248uM, respectively, which were similar to the EC50 of NMU.3. The effects of NMU2R on the expression of peptides involved in food intake...