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Analysis of enteroendocrine cell populations in the human colon

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Abstract

Recent studies have shown that patterns of colocalisation of hormones in enteroendocrine cells are more complex than previously appreciated and that the patterns differ substantially between species. In this study, the human sigmoid colon is investigated by immunohistochemistry for the presence of gastrointestinal hormones and their colocalisation. The segments of colon were distant from the pathology that led to colectomy and appeared structurally normal. Only four hormones, 5-hydroxytryptamine (5-HT), glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and somatostatin, were common in enteroendocrine cells of the human colon. Cholecystokinin, present in the colon of some species, was absent, as were glucose-dependent insulinotropic peptide, ghrelin and motilin. Neurotensin cells were extremely rare. The most numerous cells were 5-HT cells, some of which also contained PYY or somatostatin and very rarely GLP-1. Almost all GLP-1 cells contained PYY. It is concluded that enteroendocrine cells of the human colon, like those of other regions and species, exhibit overlapping patterns of hormone colocalisation and that the hormones and their patterns of expression differ between human and other species.

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References

  • Agersnap M, Rehfeld JF (2014) Measurement of nonsulfated cholecystokinins. Scand J Clin Lab Invest 74:424–431

    Article  CAS  PubMed  Google Scholar 

  • Alumets J, Sundler F, Håkanson R (1977) Distribution, ontogeny and ultrastructure of somatostatin immunoreactive cells in the pancreas and gut. Cell Tissue Res 185:465–479

    Article  CAS  PubMed  Google Scholar 

  • Andresen V, Montori VM, Keller J, West CP, Layer P, Camilleri M (2008) Effects of 5-hydroxytryptamine (Serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol 6:545–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertrand PP (2006) Real-time measurement of serotonin release and motility in guinea pig ileum. J Physiol Lond 577(2):689–704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Böttcher G, Sjölund K, Ekblad E, Håkanson R, Schwartz TW, Sundler F (1984) Coexistence of peptide YY and glicentin immunoreactivity in endocrine cells of the gut. Regul Pept 8:261–266

    Article  PubMed  Google Scholar 

  • Böttcher G, Alumets J, Håkanson R, Sundler F (1986) Co-existence of glicentin and peptide YY in colorectal L-cells in cat and man. An electron microscopic study. Regul Pept 13:283–291

    Article  PubMed  Google Scholar 

  • Buffa R, Capella C, Fontana P, Usellini L, Solcia E (1978) Types of endocrine cells in the human colon and rectum. Cell Tissue Res 192:227–240

    Article  CAS  PubMed  Google Scholar 

  • Cho H-J, Callaghan B, Bron R, Bravo DM, Furness JB (2014a) Identification of enteroendocrine cells that express TRPA1 channels in the mouse intestine. Cell Tissue Res 356:77–82

    Article  CAS  PubMed  Google Scholar 

  • Cho H-J, Robinson ES, Rivera LR, McMillan PJ, Testro A, Nikfarjam M, Bravo DM, Furness JB (2014b) Glucagon-like peptide 1 and peptide YY are in separate storage organelles in enteroendocrine cells. Cell Tissue Res 357:63–69

    Article  CAS  PubMed  Google Scholar 

  • Cho H-J, Kosari S, Hunne B, Callaghan B, Rivera LR, Bravo DM, Furness JB (2015) Differences in hormone localisation patterns of K and L type enteroendocrine cells in the mouse and pig small intestine and colon. Cell Tissue Res 359:693–698

    Article  CAS  PubMed  Google Scholar 

  • Cooke HJ, Sidhu M, Wang YZ (1997) 5-HT activates neural reflexes regulating secretion in the guinea-pig colon. Neurogastroenterol Motil 9:181–186

    Article  CAS  PubMed  Google Scholar 

  • Costa M, Furness JB (1984) Somatostatin is present in a subpopulation of noradrenergic nerve fibres supplying the intestine. Neuroscience 13:911–919

    Article  CAS  PubMed  Google Scholar 

  • Cox HM, Tough IR (2002) Neuropeptide Y, Y1, Y2 and Y4 receptors mediate Y agonist responses in isolated human colon mucosa. Br J Pharmacol 135:1505–1512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crane JD, Palanivel R, Mottillo EP, Bujak AL, Wang H, Ford RJ, Collins A, Blümer RM, Fullerton MD, Yabut JM (2015) Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Nat Med 21:166–172

    Article  CAS  PubMed  Google Scholar 

  • Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M (2000) Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 141:4255–4261

    CAS  PubMed  Google Scholar 

  • Egerod KL, Engelstoft MS, Grunddal KV et al (2012) A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Endocrinology 153:5782–5795

    Article  CAS  PubMed  Google Scholar 

  • Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman AB, Korbonits M (2002) The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87:2988–2991

    Article  CAS  PubMed  Google Scholar 

  • Gribble FM, Reimann F (2015) Enteroendocrine cells: chemosensors in the intestinal epithelium. Annu Rev Physiol 78:3.1–3.23

    Google Scholar 

  • Grider JR, Kuemmerle JF, Jin JG (1996) 5-HT released by mucosal stimuli initiates peristalsis by activating 5-HT4/5-HT1p receptors on sensory CGRP neurons. Am J Physiol 270:G778–G782

    CAS  PubMed  Google Scholar 

  • Habib AM, Richards P, Cairns LS, Rogers GJ, Bannon CAM, Parker HE, Morley TCE, Yeo GSH, Reimann F, Gribble FM (2012) Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry. Endocrinology 153:3054–3065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Helander HF, Fändriks L (2012) The enteroendocrine “letter cells” – time for a new nomenclature? Scand J Gastroenterol 47:3–12

    Article  CAS  PubMed  Google Scholar 

  • Helmstaedter V, Taugner C, Feurle GE, Forssmann WG (1977) Localization of neurotensin-immunoreactive cells in the small intestine of man and various mammals. Histochemistry 3:35–41

    Article  Google Scholar 

  • Helyes Z, Pintér E, Németh J, Kéri G, Thán M, Oroszi G, Horváth A (2001) Anti-inflammatory effect of synthetic somatostatin analogues in the rat. Br J Pharmacol 134:1571–1579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heredia DJ, Gershon MD, Koh SD, Corrigan RD, Okamoto T, Smith TK (2013) Important role of mucosal serotonin in colonic propulsion and peristaltic reflexes: in vitro analyses in mice lacking tryptophan hydroxylase 1. J Physiol Lond 591:5939–5957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hyland NP, Sjöberg F, Tough IR, Herzog H, Cox HM (2003) Functional consequences of neuropeptide Y Y2 receptor knockout and Y2 antagonism in mouse and human colonic tissues. Br J Pharmacol 139:863–871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kidd M, Modlin IM, Gustafsson BI, Drozdov I, Hauso O, Pfragner R (2008) Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants. Am J Physiol Gastrointest Liver Physiol 295:260–272

    Article  Google Scholar 

  • Kovacs TOG, Walsh JH, Maxwell V, Wong HC, Azuma T, Katt E (1989) Gastrin is a major mediator of the gastric phase of acid secretion in dogs: proof by monoclonal antibody neutralization. Gastroenterology 97:1406–1413

    Article  CAS  PubMed  Google Scholar 

  • Liu M-T, Kuan Y-H, Wang J, Hen R, Gershon MD (2009) 5-HT4 receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice. J Neurosci 29:9683–9699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Margolis KG, Stevanovic K, Li Z, Yang QM, Oravecz T, Zambrowicz B, Jhaver KG, Diacou A, Gershon MD (2014) Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut 63:928–937

    Article  CAS  PubMed  Google Scholar 

  • Mortensen K, Christensen LL, Holst JJ, Orskov C (2003) GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine. Regul Pept 114:189–196

    Article  CAS  PubMed  Google Scholar 

  • Patterson M, Murphy KG, le Roux CW, Ghatei MA, Bloom SR (2005) Characterization of ghrelin-like immunoreactivity in human plasma. J Clin Endocrinol Metab 90:2205–2211

    Article  CAS  PubMed  Google Scholar 

  • Pintér E, Helyes Z, Szolcsányi J (2006) Inhibitory effect of somatostatin on inflammation and nociception. Pharmacol Ther 112:440–456

    Article  PubMed  Google Scholar 

  • Polak JM, Pearse AGE, Bloom SR, Buchan AMJ, Rayford PL, Thompson JC (1975) Identification of cholecystokinin-secreting cells. Lancet 22:1016–1018

    Article  Google Scholar 

  • Rehfeld JF (1978) Immunochemical studies on cholecystokinin. II. Distribution and molecular heterogeneity in the central nervous system and small intestine of man and hog. J Biol Chem 253:4022–4030

    CAS  PubMed  Google Scholar 

  • Rehfeld JF (1998) Accurate measurement of cholecystokinin in plasma. Clin Chem 44:991–1001

    CAS  PubMed  Google Scholar 

  • Roth KA, Kim S, Gordon JI (1992) Immunocytochemical studies suggest two pathways for enteroendocrine cell differentiation in the colon. Am J Physiol 263:G174–G180

    CAS  PubMed  Google Scholar 

  • Rozengurt N, Wu SV, Chen MC, Huang C, Sternini C, Rozengurt E (2006) Colocalization of the α-subunit of gustducin with PYY and GLP-1 in L cells of human colon. Am J Physiol 291:G792–G802

    CAS  Google Scholar 

  • Shin A, Camilleri M, Kolar G, Erwin P, West CP, Murad MH (2014) Systematic review with meta-analysis: highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation. Aliment Pharmacol Ther 39:239–253

    Article  CAS  PubMed  Google Scholar 

  • Shulkes A, Fletcher DR, Hardy KJ (1983) Organ and plasma metabolism of neurotensin in sheep. Am J Physiol 245:457–462

    Google Scholar 

  • Sundler F, Håkanson R, Hammer RA, Alumets A, Carraway R, Leeman S, Zimmerman EA (1977) Immunohistochemical localization of neurotensin in endocrine cells of the gut. Cell Tissue Res 197:313–321

    Google Scholar 

  • Ter Beek WP, Muller ESM, Van Den Berg M, Meijer MJ, Biemond I, Lamers CBHW (2008) Motilin receptor expression in smooth muscle, myenteric plexus, and mucosa of human inflamed and noninflamed intestine. Inflamm Bowel Dis 14:612–619

    Article  PubMed  Google Scholar 

  • Walther DJ, Peter J-U, Bashammakh S, Hörtnagl H, Voits M, Fink H, Bader M (2003) Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 299:76–76

    Article  CAS  PubMed  Google Scholar 

  • van der Wielen N, van Avesaat M, de Wit NJW, Vogels JTWE, Troost F, et al. (2014) Cross-species comparison of genes related to nutrient sensingmechanisms expressed along the Intestine. PLoS ONE 9(9):e107531

  • Yanaihara N, Yanaihara C, Nagai K, Sato H, Shimizu F, Yamaguchi K, Abe K (1980) Motilin-like immunoreactivity in porcine, canine, human and rat tissues. Biomed Res 1:76–83

    CAS  Google Scholar 

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Acknowledgment

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Correspondence to John B. Furness.

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Brid Callaghan and John B Furness are equal senior authors

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Martins, P., Fakhry, J., de Oliveira, E.C. et al. Analysis of enteroendocrine cell populations in the human colon. Cell Tissue Res 367, 161–168 (2017). https://doi.org/10.1007/s00441-016-2530-7

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