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Serotonin and Gastric Health: An Overview

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Serotonin is a crucial signaling molecule in a variety of physiologic processes and pathologic symptoms of the gastrointestinal tract. Read more.

Written by

Dr. Chandana. P

Medically reviewed by

Dr. Ghulam Fareed

Published At September 21, 2023
Reviewed AtSeptember 21, 2023


Serotonin is found in the gastrointestinal mucosa's enterochromaffin cells as well as neurons in the enteric nervous system. It can be released into the blood or the gut lumen. In modern medicine, a comprehensive approach to evaluating the human body is supported by regulatory factors with multidirectional action in various organs and systems. Serotonin is a very active substance in the body. Serotonin, also known as the happiness hormone, is produced by the amino acid tryptophan through hydroxylation and decarboxylation. The diet has a significant impact on the body's serotonin levels.

What Are the Sources and Functions of Serotonin?

  • Foods high in calcium, magnesium, Vitamin B, omega-3, omega-6, and gamma linoleic acids aid in serotonin synthesis. The human body contains approximately ten grams of serotonin. Only five percent of human serotonin is found in platelets and the central nervous system (CNS).

  • Serotonin functions as a neurotransmitter in the reticular formation nuclei, hypothalamus, and limbic system. Serotonin levels in the CNS (central nervous system) influence higher nerve functions such as mood, sleep, memory, cognitive processes, and sexual and behavioral reactions.

  • Sunlight stimulates the synthesis of serotonin by epiphyseal pinealocytes. The gastrointestinal tract (GIT) contains nearly 95 percent of it, primarily in epithelial and glandular enterochromaffin (EC) cells.

Where Is Serotonin Located and Its Release?

  • The enterochromaffin cells (EC) of the intestinal mucosa appear to be the main source of serotonin in the body. Immunohistochemically, serotonin-containing cells are located at the base of the small intestine's crypts and villi.

  • Human studies have revealed that serotonin is released into the portal circulation by the stimulation of the vagal and splanchnic nerves. Serotonin is also released into the lumen of the gut as a result of vagal stimulation. Thus, serotonin extrinsic neuronal release may activate both local and hormonal effects of the amine.

  • Myenteric and submucosal plexus nerve fibers contain very little serotonin. Mast cells present in the gastrointestinal wall contain 10 percent of the serotonin in the tube.

  • Serotonin, as a gastrointestinal hormone, regulates the motor activity of the smooth muscles and glandular secretion. It has an effect on gastrointestinal sensations such as pain, nausea, and vomiting.

  • Serotonin, which is found in platelets and mast cells, is a very powerful vasoconstrictor and an active factor in the processes of hemostasis, inflammation, and allergic reactions. Serotonin functions through specific receptors.

What Are the Effects of Serotonin on Gastric Acid Secretion?

  • Central or peripheral administration of serotonin works by inhibiting acid secretion in a variety of species. Serotonin inhibited basal acid secretion and pepsin output in conscious gastric fistula rats.

  • Serotonin inhibited histamine and pentagastrin-stimulated acid secretion in the isolated rat stomach preparation without affecting basal stimulated secretion. Methysergide and Indomethacin both inhibited the serotonin response, indicating that there may be more than one mechanism of action.

  • In humans, Methysergide increased basal and pentagastrin-stimulated acid secretion while metergoline inhibited it, generating questions about the role of endogenous serotonin in gastric secretion.

  • Serotonin seems to block gastric acid secretion and may act as an enterogastrone.

What Are the Effects of Serotonin Mucus Output?

  • Black and colleagues proposed that a physiologic function of serotonin in the GI tract has the potential to stimulate the production of a protective mucous lining.

  • These researchers discovered that serotonin, 5-hydroxytryptophan, and L-tryptophan increase the luminally perfused rat colon's hexose output. Chlorpromazine and Methysergide, both of which acted as agonists, inhibited the effect.

  • Previous studies found that intravenous serotonin increased gastric mucus output while decreasing histamine-stimulated acid secretion. It has been proposed that serotonin's mucus-stimulating property is not dependent on its motility-enhancing effect.

What Are the Effects of Serotonin on Intestinal Transport?

  • Serotonin is well known for causing net water and electrolyte secretion in the small intestine. These alterations do not accompany the changes in enterocyte adenylate cyclase, cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) content.

  • Serotonin added to the serosal solution causes a marked increase in short-circuit current in vitro using chamber studies. This response is caused by an inhibition of Na and chloride mucosal-to-serosal flux and an increase in net chloride secretion.

  • Serotonin increases short-circuit current in vitro by decreasing net sodium and chloride absorption. The decrease in net chloride absorption is greater than the absorption of sodium.

  • Again, removing calcium from the serosal solution prevents all serotonin effects, whereas tetrodotoxin, a neurotransmission inhibitor, has no effect on serotonin-induced electrolyte transport changes.

  • These findings show that serotonin influences water and electrolyte flux in the small and large intestines by altering enterocyte plasma membrane permeability to calcium ions.

  • Recently, the function of serotonin in amebiasis diarrhea has been reported. When Entamoeba histolytica lysates were positioned on the serosal side of epithelial sheets of rabbit ileum or rat colon, a substantial improvement in short circuits current was observed.

  • This calcium-dependent response was blocked partially by the serotonin antagonist bufotenin or a serotonin antibody. Also, the lysates resemble the effects of serotonin on intestinal secretion, but serotonin was also found in the lysates. This evidence supports the intriguing hypothesis that serotonin is a mediator of amebiasis diarrhea.

What Are the Effects of Serotonin on Motility?

  • Serotonin has direct and indirect, excitatory, and inhibitory effects on gastrointestinal smooth muscle based on the location of the gastrointestinal tract.

  • Serotonin has been linked to vagally mediated receptive relaxation in the guinea pig stomach, largely through a neural mechanism. Exogenous serotonin administration to a conscious dog causes a significant rise in contractions of the circular muscles, similar to phase one of the migrating motor complex in the jejunum and ileum.

  • The response to serotonin was lowered after tetrodotoxin in Burks' preparation, demonstrating a significant intrinsic neural component to the response.

  • Experiments on the ileum of the guinea pig support the idea that serotonin's primary action in the intestine is a neuronal action, with a little direct effect on longitudinal smooth muscle and almost no direct effect on ileal circular smooth muscle.

  • Costa and Furness conclude that serotonin stimulates:

1. Excitatory cholinergic nerves.

2. Excitatory noncholinergic nerves.

3. Inhibitory noncholinergic nerves in the guinea pig intestine.

What Are the Effects on Mesenteric Blood Flow?

  • The effect of serotonin on mesenteric circulation seems to be dependant on the dose, preparation, species, and motor activity-dependent.

Is Serotonin a Pivotal Mechanism in Irritable Bowel Syndrome (IBS)?

  • Given that the gut contains 95 percent of the serotonin in the body, it stands to reason that postprandial plasma levels of (5-HT) 5-hydroxytryptamine are derived from the gut.

  • Reports of plasma 5-HT concentrations in various functional gastrointestinal disorders indicate that circulating serotonin may be involved in determining predominant bowel function: serotonin levels are higher in diarrhea and celiac disease and lower in constipation.


Serotonin and serotonergic agents will remain important in the mechanisms and treatment of gastrointestinal diseases, particularly lower functional gastrointestinal disorders. The expression of the 5-hydroxytryptamine receptor 3 serotonin receptor in epithelial, glandular, and interstitial cells suggests that serotonin can influence the secretion of the gastric mucosa and mobility of the gastrointestinal tract.

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Dr. Ghulam Fareed
Dr. Ghulam Fareed

Medical Gastroenterology


serotonin and gastric health
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