'Thin pill' is years away

“A pill that makes obese people feel full up after eating just a small meal could be on the way”, according to The Sun . The Daily Telegraph said that researchers have found a way to stop the stomach expanding, thereby limiting the amount of food that can be digested.

The Daily Mail explained that the discovery involves two cell proteins - P2Y1 and P2Y11 - which cause the stomach to expand slowly after eating, “allowing its capacity to increase 25-fold from three fluid ounces to around four pints". All the stories quote the researchers as saying that a pill that could block these protein receptor cells would act the same way as a gastric band.

This study involved a set of experimental studies on guinea pigs and, specifically, two proteins that act as receptors and pick up nerve signals that control the size of the large bowel. This new approach to treating obesity with drugs is still at a preliminary stage and will require years of further research before reaching a stage where its effect and safety in humans can begin to be tested.

The most effective way to lose weight and maintain a healthy weight is with a balanced diet and a regular, effective amount of physical activity.

Where did the story come from?

Dr Brian King and Andrea Townsend-Nicholson from the Departments of Physiology and Biochemistry and Molecular biology at University College London carried out the research. The investigators were partly supported by the British Heart Foundation. The study was published in the peer-reviewed: The Journal of Pharmacology and Experimental Therapeutics.

What kind of scientific study was this?

This was a report of a set of experimental studies that investigated two groups of proteins called P2X and P2Y receptors. These receptors are involved in a process called “purinergic signalling” which controls the smooth muscles in the gut , specifically its ability to relax.

Using the smooth muscle that occurs in bands along the colon (large bowel) of the guinea pig the researchers identified the genes that code for two different kinds of P2Y receptors (P2Y1 and P2Y11). They then looked at where the receptor proteins were located in the muscle tissue in the laboratory.

The researchers removed muscle strips from the colons of the guinea pigs. The tension in the muscle was measured by  a device that measures how much something can be stretched or compressed. The researchers were particularly interested in the fast and slow relaxations that result when the purinergic receptors are activated.

The researchers then tested the speed and extent of relaxation in the muscle while the strips were immersed in different experimental solutions that either activated or inhibited the receptors.

What were the results of the study?

The researchers’ experiments showed that the smooth muscle cells in the muscle strips extracted from guinea pig colon, possess the two P2Y receptors sub types P2Y1 and P2Y11, while nerve cells within the muscle possess the two P2X receptors sub types P2X2 and  P2X3.

The two P2Y receptors mediate fast and slow purinergic relaxations of the muscle, and are facilitated by the P2X receptors. They found that the action of a selection of purinergic nucleotides, including ATP (adenosine triphosphate) caused fast relaxation of smooth muscle cells. Lastly, they showed that this relaxation can be blocked by the receptor antagonist, a chemical known as MRS2179.

What interpretations did the researchers draw from these results?

The researchers conclude that “two different P2Y receptors occur on colonic [smooth muscle cells] and that they elicit fast or slow relaxations depending on local conditions.”  The researchers were able to control the speed of relaxations in the muscle by altering the chemical solution surrounding the tissue.

They also found that P2X receptors on nerves stimulate ATP release, thereby suggesting a mechanism for the relaxation. They claim that their research has extended knowledge about “the pharmacology of P2Y11 receptors” and that this will further an understanding of the actions of these chemicals in smooth muscle.

What does the NHS Knowledge Service make of this study?

This is a laboratory experiment in physiology and biochemistry that may have implications for drug development in the future.

Although the research paper points out that the two proteins that were identified are similar to those found in humans, a considerable amount of work is needed before it is possible to ascertain if it is possible to safely block them in humans. As the researchers clearly point out, a decade of further study will be required before any potential drug reaches the market.

NHS Attribution