Research Description

Investigating Possible Differences in the Melanocortin Receptors' Intracellular Signaling Pathways

The melanocortin system consists of five known G-protein coupled receptors, which are known to stimulate the cyclic adenosine monophosphate (cAMP) signal transduction pathway. Several of its naturally occurring agonists and antagonists are known to regulate a variety of physiological functions. The melanocortin-3 and -4 receptors (MC3R and MC4R respectively) have been implicated in the regulation of energy and weight homeostasis. In feeding studies, the injection of a melanocortin receptor agonist compound reduces the amount of food consumption, while the injection of an antagonist compound results in an increase in the amount of food an animal will eat. However, if a receptor is mutated, it will sometimes respond to agonists and antagonists differently. For instance, approximately four percent of obese children have a polymorphism of the MC4R, causing them to remain hungry when they should feel full.

This project will test the hypothesis that the various melanocortin receptors have differences in intracellular signaling. To accomplish this goal, cell cultures expressing one of the human melanocortin receptors will be grown and then stimulated by an agonist or antagonist over a range of concentrations. After stimulation, the cell samples will be lysed, filtered, and frozen. The samples will then be tested using a Luminex machine and a variety of kits to determine which intracellular signaling components were affected and in what way. By distinguishing between the pathways that are activated by the various melanocortin receptors, this research could be used to develop drugs that would help individuals with melanocortin receptor polymorphisms or altered signaling pathways maintain a normal weight and level of energy.