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.

1.
Boularand S, Darmon MC, Mallet J: The human tryptophan hydroxylase gene. An unusual splicing complexity in the 5′-untranslated region. J Biol Chem 1995;270:3748–3756.
[PubMed]
2.
Stoll J, Kozak CA, Goldman D: Characterization and chromosomal mapping of a cDNA encoding tryptophan hydroxylase from a mouse mastocytoma cell line. Genomics 1990;7:88–96.
[PubMed]
3.
Lovenberg W, Jequier E, Sjördsma A: Tryptophan hydroxylation. Measurement in pineal gland, brainstem, and carcinoid tumor. Science 1967;155:217–219.
[PubMed]
4.
Noguchi T, Nishino M, Kido R: Tryptophan 5-hydroxylase in rat intestine. Biochem J 1973;131:375–380.
[PubMed]
5.
Tipper JP, Citron BA, Ribeiro P, Kaufman S: Cloning and expression of rabbit and human brain tryptophan hydroxylase cDNA in Escherichia coli. Arch Biochem Biophys 1994;315:445–453.
[PubMed]
6.
D’Sa CM, Arthur RE, Kuhn DM: Expression and deletion mutagenesis of tryptophan hydroxylase fusion proteins. Delineation of the enzyme catalytic core. J Neurochem 1996;67:917–926.
[PubMed]
7.
D’Sa CM, Arthur RE, States JC, Kuhn DM: Tryptophan hydroxylase. Cloning and expression of the rat brain enzyme in mammalian cells. J Neurochem 1996;67:900–906.
[PubMed]
8.
Gilbert JA, Bates LA, Ames MM: Elevated aromatic L-amino acid decarboxylase in human carcinoid tumors. Biochem Pharmacol 1995;50:845–850.
[PubMed]
9.
Hasegawa H, Yanagisawa M, Inoue F, Yanaihara N, Ichiyama A: Demonstration of non- neural tryptophan 5-mono-oxygenase in mouse intestinal mucosa. Biochem J 1987;248:501–509.
[PubMed]
10.
Bertaccini G: Tissue 5-hydroxytryptamine and urinary 5-hydroxyindoleacetic acid after partial or total removal of the gastrointestinal tract in the rat. J Physiol 1960;153:239–249.
11.
Cetin Y: Enterochromaffin cells of the mammalian gastro-entero-pancreatic endocrine system. Cellular source of pro-dynorphin-derived peptides. Cell Tissue Res 1988;253:173–179.
[PubMed]
12.
Larsson LI, Jorgensen LM: Ultrastructural and cytochemical studies on the cytodifferentiation of duodenal endocrine cells. Cell Tissue Res 1978;194:79–102.
[PubMed]
13.
Fujimiya M, Okumiya K, Yamane T, Maeda T: Distribution of serotonin-immunoreactive nerve cells and fibers in the rat gastrointestinal tract. Histochem Cell Biol 1997;107:105–114.
[PubMed]
14.
Kobayashi T, Hasegawa H, Kaneko E, Ichiyama A: Gastrointestinal serotonin. Depletion due to tetrahydrobiopterin deficiency induced by 2,4-diamino-6-hydroxypyrimidine administration. J Pharmacol Exp Ther 1991;256:773–779.
[PubMed]
15.
Cohn DV, Elting JJ, Frick M, Elde R: Selective localization of the parathyroid secretory protein-I/adrenal medulla chromogranin A protein family in a wide variety of endocrine cells of the rat. Endocrinology 1984;114:1963–1974.
[PubMed]
16.
Rindi G, Buffa R, Sessa F, Tortora O, Solcia E: Chromogranin A, B and C immunoreactivities of mammalian endocrine cells. Distribution, distinction from costored hormones/prohormones and relationship with the argyrophil component of secretory granules. Histochemistry 1986;85:19–28.
[PubMed]
17.
Hakanson R, Lombard des Gouttes MN, Owman C: Activities of tryptophan hydroxylase, dopa decarboxylase, and monoamine oxidase as correlated with the appearance of monoamines in the developing pineal gland. Life Sci 1967;6:2577–2585.
[PubMed]
18.
Facer P, Polak JM, Jaffe BM, Pearse AGE: Immunocytochemical demonstration of 5-hydroxytryptamine in gastrointestinal endocrine cells. Histochem J 1979;11:117–121.
[PubMed]
19.
Racké K, Schwörer H: Characterization of the role of calcium and sodium channels in the stimulus secretion coupling of 5-hydroxytryptamine release from porcine enterochromaffin cells. Naunyn Schmiedebergs Arch Pharmacol 1993;347:1–8.
[PubMed]
20.
Schwörer H, Racké K, Kilbinger H: Spontaneous release of endogenous 5-hydroxytryptamine and 5-hydroxyindoleacetic acid from isolated vascularly perfused ileum of the guinea pig. Neuroscience 1987;21:297–303.
[PubMed]
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