Investigating how sensory gut cells communicate
A group of sensory cells in the intestine known as enteroendocrine cells (EECs) can sense changes such as nutrients arriving in the gut and respond by secreting signalling molecules called neurotransmitters as well as hormones. “EECs are secretory cells that can sense changes in the gut lumen. It is important to gain a better understanding of the fundamental processes by which these cells translate sensory signals into a chemical response and transmit the information further to the brain and other cells in the body,” explains Cordelia Imig, associate professor at the University of Copenhagen who led the research on the SynGut project with the support of the Marie Skłodowska-Curie Actions programme. Characterising the function of different EEC types and how they control neurotransmitter and hormone release can help in understanding their role in human disorders such as diabetes and inflammatory bowel diseases, she notes.
Investigating the release of serotonin in the gut
The project focused on serotonergic enterochromaffin cells that form the largest EEC subclass and can be found in all gut regions. These cells signal through the neurotransmitter serotonin which is also known to be an important neuromodulator in the brain. Gastrointestinal serotonin is important for regulating physiological processes such as the process by which food travels through the intestine, and may serve, in addition, as a fast-acting satiety signal to the brain. “Enterochromaffin cells in the gut have been shown in previous studies to come into close contact with neurons that signal to the brain,” Imig adds. “In this project, we wanted to understand whether these cells signal to neurons through the same process and with similar speed as communication taking place in the brain, or whether this process is slower and more comparable to endocrine cells such as insulin-secreting cells in the pancreas or chromaffin cells of the adrenal gland.”
Monitoring serotonin release with high spatial and temporal resolution
The SynGut project used a multidisciplinary approach to study various aspects of enterochromaffin cell function and cell biology. “To get the spatial and temporal resolution required investigating enterochromaffin cells, so we needed to set up ways to monitor secretion from individual cultured cells,” she remarks. The team employed a technique called carbon-fibre amperometry to detect tiny amounts of serotonin released from individual enterochromaffin cells. “Using this technique, we found that cultured enterochromaffin cells release serotonin much slower than neurons would in the brain,” says Imig. “The release process closely resembles that of other neurosecretory cell types such as adrenal chromaffin cells that secrete adrenaline and noradrenaline, important for the fight-or-flight response.” The finding that it has similarities to other endocrine cells has implications for understanding how fast, and via which routes, signals from the gut may be transmitted to the brain. “Our results opened up a lot of questions that we still need to address in the future. Our ultimate goal is to understand the molecular mechanisms that regulate serotonin release from enterochromaffin cells, which may help to identify potential new molecular targets to treat disorders that are linked to abnormal enterochromaffin cell function.”
Keywords
SynGut, diabetes, gut, intestine, bowel, neurotransmitters, hormones, enteroendocrine cells, enterochromaffin cells, serotonin, neurons
