Differential Distribution of Serotonin and Tryptophan Hydroxylase in the Human Gastrointestinal Tract

Abstract

The distribution of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin, was investigated immunohistochemically in various organs of the gastrointestinal tract and compared with that of neuroendocrine markers. While immunoreactivity for serotonin and chromogranin A was restricted to enterochromaffin cells, positive staining for tryptophan hydroxylase was detected in normal enterocytes lining the epithelium of the small intestine. Tryptophan hydroxylase was localized in the supranuclear cytoplasm of absorptive cells, and was absent from the terminal web. The enterocytes of the exfoliation zone at the tips of the villi demonstrated a strong immunoreactivity similar to those at the slope of the villi. Mucus-containing Goblet cells, Paneth cells and stromal cells of the lamina propria remained unlabelled. The duodenal glands of Brunner revealed only sporadically a weak immunostaining for tryptophan hydroxylase. The monooxygenase was also detected in numerous secretory tubules of the pyloric mucosa, where the proportion of positive cells decreased progressively from the crypts towards the upper parts of the gastric glands. No significant immunoreactivity was demonstrated in colon, adrenal cortex, liver, pancreas, and mesenteric lymph nodes. The demonstration of tryptophan hydroxylase in normal enterocytes suggested that epithelial cells of the small intestine are able to synthesize 5-hydroxytryptophan.

Role of a Serotonin Precursor in Development of Gut Microvilli

“…Similar to our results, the differentiated villous epithelial cells displayed an intense immunoreactivity for anti-TPH antibody in the human duodenum. 34 Consistently, we found observations suggesting subtle 5-HT synthesis in Caco-2 cells. SP, a BH4 precursor, increases cellular BH4 levels much more effectively than BH4 itself when used as the supplement.…”

Indole is an inter-species biofilm signal mediated by SdiA

“…Other hormones are also present in the gastrointestinal tract including melatonin [51] and serotonin [52]; both are neural hormones which maintain homeostasis and both reduce chlamydial infection [53]. In addition, plants use indole 3-acetic acid as their main hormone (for cell growth, division, tissue differentiation, and response to light and gravity), and bacteria interrupt this eucaryotic signaling by using indole-3-acetic acid as a source of carbon, nitrogen, and energy [54].…”

Serotonin and Blood Pressure Regulation

“…However, it is not clear whether the adrenal gland-cortex or medulla-can synthesize 5-HT. In the human, TPH was not detected immunohistochemically in the adrenal cortex (Meyer and Brinck 1999). An interesting connection between adrenal gland and brain 5-HT synthesis was made by Miller et al (1980), who demonstrated that brain tryptophan utilization was determined by the presence or absence of the adrenal gland.…”