Cell proteins could offer a future drug target against weight gain

Two cell proteins that relax the gut and help accommodate a big meal have been identified by UCL (University College London) scientists.

The proteins could offer a future drug target against weight gain, by preventing the stomach from expanding.

In a paper published in this month's issue of the Journal of Pharmacology and Experimental Therapeutics, Dr Brian King and Dr Andrea Townsend-Nicholson explored the molecular basis of relaxations of the gut. In the study, the authors identified two protein receptors – P2Y1 and P2Y11 – involved in fast and slow relaxations of the gut. These proteins were identified in the guinea pig, but are also present in the human gut, and thus offer the potential as a future target for drug treatment. Further research by the UCL team will focus on the human isoform of the P2Y11 protein receptor.

Dr Brian King of the UCL Department of Neuroscience, Physiology and Pharmacology says: “The mechanisms we have identified are important to the normal workings of the stomach - a hollow organ which actively relaxes to help accommodate the size of your meal. The human stomach has a ‘resting' internal volume of 75 millilitres but, by relaxing its muscular wall, can expand to an internal volume of two litres or more - a 25-fold increase in the volume it can accept. This expansion is controlled by nerves inside the stomach wall and these nerves release molecules that stimulate the P2Y1 and P2Y11 receptor proteins embedded in muscle cells in the gut wall.

“The mechanism of slow relaxation of the stomach might represent a future drug target in the fight to control weight gain and reverse obesity. We are looking to identify drugs that would block the P2Y11 receptor and, therefore, prevent slow relaxation of the stomach. As a result of blocking the P2Y11-based mechanism, meal size would be smaller, offering the person a better chance of regulating their food intake.

“This would be a brand new approach to weight control. At present, the most successful way to help obese patients lose weight is gastric banding or stomach stapling, both of which reduce the maximum volume of the stomach. But these are also tricky surgical procedures, not without attendant risks. A pill that could replace this surgery, yet have the same effect, might be a useful alternative.”