EAST LANSING, Mich. - Researchers at Michigan State University have discovered a previously unknown interaction between nerve cell receptors in the digestive tract that could lead to new treatments for a variety of common gastrointestinal problems.
Gastrointestinal motility disorders - including chronic indigestion, constipation, diarrhea and irritable bowel syndrome - are among the most frequently cited reasons for doctor visits in the United States. These disorders can be attributed partly to changes in the way that nerves influence contractions and relaxations of the muscles in the digestive tract. Although gastrointestinal motility disorders are common, little is known about how nerves control the digestive tract.
In a study published today in the science journal Nature, researchers from MSU and the California Institute of Technology present their discovery of a new mechanism by which the unique nerve cells of the digestive tract "talk" to each other and affect the digestion process.
"Understanding how these nerve cells interact is an exciting research area with broad implications for the management of a number of gastrointestinal disorders," said James J. Galligan, professor of pharmacology and toxicology in the MSU College of Human Medicine and one author of the study.
The activity of the digestive tract is controlled by the enteric nervous system, or "little brain" of the gut. The little brain is a group of nerve cells that live comfortably between the muscle layers of the digestive tract. The little brain controls contractions and relaxations of the stomach and intestines, performing these tasks without input from the brain or spinal cord.
Nerve cells converse by releasing special chemicals called neurotransmitters. The neurotransmitters attach to specific proteins, called receptors, on nerve cells receiving the incoming message. Two important neurotransmitters released by nerve cells in the little brain are acetylcholine and adenosine triphosphate (ATP). When these neurotransmitters bind to their own receptors, they excite or turn on the nerves receiving the signal.
The conventional thinking about receptors is that they transmit their signals without interference from other receptors that are nearby in the membrane of the nerve cell.
However, the work of Galligan's research team and collaborators at Cal Tech suggests that this conventional thinking may be incorrect, at least as far as receptors for acetylcholine and ATP are concerned. This work shows that when acetylcholine attaches to its receptor it blocks the excitatory signal coming from the ATP receptor.
Furthermore, when ATP attaches to its receptor, this combination blocks the excitatory signal coming from the acetylcholine receptor. These results demonstrate that there is "cross-talk" between receptors for different neurotransmitters.
This cross-talk occurs in cells that normally do not make receptors for acetylcholine or ATP but are induced artificially to make these receptors. Importantly, cross-talk also occurs in nerve cells of the little brain. Studies are currently under way that will determine how this cross-talk actually occurs. For example, do the acetylcholine and ATP receptors bump into one another in the membrane or is there another protein that connects these receptors and transmits an inhibitory signal between them?
"Everyone is fascinated by the complexity of the nerve cell organization in the brain that allows us to remember events that happened many years ago or to picture what our lives might be like in the future," Galligan said. "It seems that the organization of the little brain is also complex. It is possible that subtle changes in the way in which nerve cells of the little brain converse lead to more dramatic changes in the way the digestive tract behaves.
"It is clear that understanding how the little brain works normally will help us understand what happens when it is not working normally. This better understanding will aid in the development of new drug or other treatments for constipation, diarrhea, indigestion or irritable bowel syndrome.
"Based on this research it also becomes more likely that these treatments would have a specific action on the little brain without having unwanted side effects on the central nervous system, including the big brain."