Study On The Influence On ERK Pathway By The Co-activation Of Melanocortin-3 Receptor And D2-dopamine Receptor

At present,the world is facing a serious obesity problem.Obesity is the chief culprit of a series of diseases,which will not only cause great harm to people’s health,but also seriously affect people’s normal life.Therefore,the prevention and treatment of obesity has extensive social significance.Obesity is caused by the imbalance of energy regulation in the body.The hypothalamic melanocortin system plays an important role in weight maintenance and energy regulation.Melanocortin receptor-3(MC3R)and its family sub-type MC4 R are involved in the regulation of energy metabolism.Some studies have found that the central melanocortin system may also affect the activity of other brain regions such as the mesolimbic dopamine system.It is suspected that the central melnocortin system highly possibly regulates feeding behavior through the reward circuit,thus affecting the energy balance.The important receptor in the reward circuit is D2-dopamine receptor(D2R),which has been studied on the association between D2 R and obesity.It has been proved that MC3 R and D2 R co-express in the ventral tegmental area(VTA)of the midbrain.Thus,in this study,co-expression systems of MC3 R gene and D2 R gene were constructed by transient transfection in HEK293 T cells.MC3 R endogenous agonist α-MSH and D2 R agonist dopamine were used to activate the two receptors.Western Blot was applied to compare the phosphorylation levels of ERK1/2 to explore whether MC3 R and D2 R interact directly at the receptor level,and whether the interaction can produce unique physiological effects on MAPK pathway.The results showed that the two receptors when co-expressed still had the ability of activation,and the phosphorylation level of ERK1/2 co-activated by the two receptors had no significant difference from that of the two receptors expressed and activated alone.Compared with other agonist-activated groups,when D2 R was co-expressed with MC3 R and activated by dopamine alone,the phosphorylation level of ERK1/2 significantly decreased,which suggested that there was direct interaction between MC3 R and D2 R,and that the function of D2 R had been inhibited to a certain extent due to the interaction.