P&S Journal: Fall 1996, Vol.16, No.3
Serotonin and Digestion
Researchers have identified a molecule in the digestive system that inactivates secreted serotonin (5-HT, 5-hydroxytryptamine). The discovery of the molecule, a transmembrane 5-HT transporter identical to one found in the brain, was the latest in a series of crucial pieces of evidence supporting the role of a serotonergic system in controlling peristalsis in the digestive tract. "We have postulated that serotonin was responsible for initiating and propagating the peristaltic reflex, but without an inactivating mechanism we couldn't say for sure that 5-HT served this function," says Dr. Michael D. Gershon, professor and chairman of anatomy and cell biology. The finding has implications for the control of gastrointestinal side effects of drugs aimed at serotonin receptors in the brain and, more importantly, for the development of new drugs to treat ailments of both gut and brain.
In a paper published in an April issue of The Journal of Neuroscience, Dr. Gershon; Dr. Paul R. Wade, associate research scientist in anatomy and cell biology; and researchers from Tulane and Vanderbilt universities identified the molecule in the gut and demonstrated that blocking the 5-HT transporter dramatically affected colonic motility.
In previous work, Dr. Gershon and many others have found the GI tract contains a virtual second brain, complete with "huge numbers" of neurons equipped with receptors for all of the classes of neurotransmitter also found in the brain. These findings, along with the current research, demonstrate that many drugs aimed at the brain may also affect the GI tract. For instance, the gastrointestinal side effects of fluoxetine (Prozac) and other selective serotonin reuptake inhibitors are the direct effects of fluoxetine on the gut's serotonin transporter.
In addition to serotonin receptors, GI receptors for other neurotransmitters also could be affected by various medicines. "There are a whole range of compounds that deal with psychoses and psychoneuroses that have not been tried for GI disease but that could possibly have beneficial effects on such diseases," says Dr. Gershon.
Likewise, says Dr. Wade, compounds used to treat GI problems, such as medications to treat functional bowel disorders, in which GI motility is abnormal, might have effects in the central nervous system. The researchers are now working on the details of how pressure and chemical stimuli release the serotonin that activates intrinsic sensory nerves to initiate enteric reflexes.