Skip to main content
SpringerLink
Log in

Integrated Neural and Endocrine Control of Gastrointestinal Function

  • Chapter
  • First Online:
Book cover The Enteric Nervous System

Part of the book series: Advances in Experimental Medicine and Biology ((ANS,volume 891))

Abstract

The activity of the digestive system is dynamically regulated by external factors, including body nutritional and activity states, emotions and the contents of the digestive tube. The gut must adjust its activity to assimilate a hugely variable mixture that is ingested, particularly in an omnivore such as human for which a wide range of food choices exist. It must also guard against toxins and pathogens. These nutritive and non-nutritive components of the gut contents interact with the largest and most vulnerable surface in the body, the lining of the gastrointestinal tract. This requires a gut sensory system that can detect many classes of nutrients, non-nutrient components of food, physicochemical conditions, toxins, pathogens and symbionts (Furness et al., Nat Rev Gastroenterol Hepatol 10:729–740, 2013). The gut sensors are in turn coupled to effector systems that can respond to the sensory information. The responses are exerted through enteroendocrine cells (EEC), the enteric nervous system (ENS), the central nervous system (CNS) and the gut immune and tissue defence systems. It is apparent that the control of the digestive organs is an integrated function of these effectors. The peripheral components of the EEC, ENS and CNS triumvirate are extensive. EEC cells have traditionally been classified into about 12 types (disputed in this review), releasing about 20 hormones, together making the gut endocrine system the largest endocrine organ in the body. Likewise, in human the ENS contains about 500 million neurons, far more than the number of neurons in the remainder of the peripheral autonomic nervous system. Together gut hormones, the ENS and the CNS control or influence functions including satiety, mixing and propulsive activity, release of digestive enzymes, induction of nutrient transporters, fluid transport, local blood flow, gastric acid secretion, evacuation and immune responses. Gut content receptors, including taste, free fatty acid, peptide and phytochemical receptors, are primarily located on EEC. Hormones released by EEC act via both the ENS and CNS to optimise digestion. Toxic chemicals and pathogens are sensed and then avoided, expelled or metabolised. These defensive activities also involve the EEC and signalling from EEC to the ENS and the CNS. A major challenge is to develop a comprehensive understanding of the integrated responses of the gut, via its effector systems, the ENS, extrinsic innervation, EEC and the gut immune system, to the sensory information it receives.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Basso N, Improta G, Melchiorri P, Sopranzi N (1974) Gastrin release by bombesin in the antral pouch dog. Rendic Gastroenterol 6:95–98

    Google Scholar 

  • Böttcher G, Ahrén B, Lundquist I, Sundler F (1989) Peptide YY: intrapancreatic localization and effects on insulin and glucagon secretion in the mouse. Pancreas 4:282–288

    Article  PubMed  Google Scholar 

  • Brubaker PL (2012) A beautiful cell (or two or three?). Endocrinology 153:2945–2948

    Article  CAS  PubMed  Google Scholar 

  • Brubaker PL, Anini Y (2003) Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. Can J Physiol Pharmacol 81:1005–1012

    Article  CAS  PubMed  Google Scholar 

  • Brubaker PL, Izzo AA, Hill M, Drucker DJ (1997) Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2. Am J Physiol 272:E1050–E1058

    CAS  PubMed  Google Scholar 

  • Buchman AL, Katz S, Fang JC, Bernstein CN, Abou-Assi SG (2010) Teduglutide, a novel mucosally active analog of glucagon-like peptide-2 (GLP-2) for the treatment of moderate to severe Crohn’s disease. Inflamm Bowel Dis 16:962–973

    Article  PubMed  Google Scholar 

  • Cani PD, Possemiers S, Van de Wiele T et al (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58:1091–1103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cannon WB (1907) Oesophageal peristalsis after bilateral vagotomy. Am J Physiol 19:436–444

    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 et al (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 

  • Cox HM (2007) Peptide YY: a neuroendocrine neighbor of note. Peptides 28:345–351

    Article  CAS  PubMed  Google Scholar 

  • De Giorgio R, Guerrini S, Barbara G et al (2004) Inflammatory neuropathies of the enteric nervous system. Gastroenterology 126:1872–1883

    Article  PubMed  Google Scholar 

  • de Groat WC, Nadelhaft I, Milne RJ, Booth AM, Morgan C, Thor K (1981) Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine. J Auton Nerv Syst 3:135–160

    Article  PubMed  Google Scholar 

  • Di Nardo G, Blandizzi C, Volta U et al (2008) Review article: molecular, pathological and therapeutic features of human enteric neuropathies. Aliment Pharmacol Ther 28:25–45

    Article  PubMed  Google Scholar 

  • Dockray GJ (2013) Enteroendocrine cell signalling via the vagus nerve. Curr Opin Pharmacol 13:1–5

    Article  Google Scholar 

  • Dragstedt LR (1945) Vagotomy for gastroduodenal ulcer. Ann Surg 122:973–989

    Article  PubMed Central  Google Scholar 

  • Drucker DJ, Ehrlich P, Asa SL, Brubaker PL (1996) Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci U S A 93:7911–7916

    Article  CAS  PubMed  PubMed Central  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 

  • Engelstoft MS, Egerod KL, Holst B, Schwartz TW (2008) A gut feeling for obesity: 7TM sensors on enteroendocrine cells. Cell Metab 8:447–449

    Article  CAS  PubMed  Google Scholar 

  • Engelstoft MS, Egerod KL, Lund ML, Schwartz TW (2013) Enteroendocrine cell types revisited. Curr Opin Pharmacol 13:912–921

    Article  CAS  PubMed  Google Scholar 

  • Furness JB (2006) The enteric nervous system. Blackwell, Oxford

    Google Scholar 

  • Furness JB (2012) The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 9:286–294

    Article  CAS  PubMed  Google Scholar 

  • Furness JB, Costa M (1974) The adrenergic innervation of the gastrointestinal tract. Ergeb Physiol 69:1–51

    CAS  Google Scholar 

  • Furness JB, Rivera LR, Cho H-J, Bravo DM, Callaghan B (2013) The gut as a sensory organ. Nat Rev Gastroenterol Hepatol 10:729–740

    Article  CAS  PubMed  Google Scholar 

  • Geraedts MCP, Takahashi T, Vigues S et al (2012) Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery. Am J Physiol 303:E464–E474

    CAS  Google Scholar 

  • Gwynne RM, Ellis M, Sjövall H, Bornstein JC (2009) Cholera toxin induces sustained hyperexcitability in submucosal secretomotor neurons in guinea pig jejunum. Gastroenterology 136:299–308

    Article  PubMed  Google Scholar 

  • Habib AM, Richards P, Cairns LS et al (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 

  • Hasler WL (2003) Physiology of gastric motility and gastric emptying. In: Yamada T (ed) Gastroenterology. Lippincott Williams & Wilkins, Philadelphia, pp 195–219

    Google Scholar 

  • Holst JJ (2007) The physiology of glucagon-like peptide 1. Physiol Rev 87:1409–1439

    Article  CAS  PubMed  Google Scholar 

  • Holst JJ, Knuhtsen S, Orskov C, Skak-Nielsen T, Poulsen SS, Jensen SL, Nielsen OV (1987) GRP nerves in pig antrum: role of GRP in vagal control of gastrin secretion. Am J Physiol 253:G643–G649

    CAS  PubMed  Google Scholar 

  • Hsieh J, Longuet C, Maida A et al (2009) Glucagon-like peptide-2 increase intestinal lipid absorption and chylomicron production via CD36. Gastroenterology 137:997–1005

    Article  CAS  PubMed  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 

  • Ingelfinger FJ (1958) Esophageal motility. Physiol Rev 38:533–584

    CAS  PubMed  Google Scholar 

  • Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O'Keefe SJ (2011) Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut 60:902–914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knowles CH, De Giorgio R, Kapur RP et al (2010) The London classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group. Gut 59:882–887

    Article  PubMed  Google Scholar 

  • Kumar A (2012) Second line therapy: type 2 diabetic subjects failing on metformin GLP-1⁄DPP-IV inhibitors versus sulphonylurea/insulin: for GLP-1⁄DPP-IV inhibitors. Diabetes Metab Res Rev 28:21–25

    Article  PubMed  Google Scholar 

  • Lundgren O (2002) Enteric nerves and diarrhoea. Pharmacol Toxicol 90:109–120

    Article  CAS  PubMed  Google Scholar 

  • Lynch AC, Antony A, Dobbs BR, Frizelle FA (2001) Bowel dysfunction following spinal cord injury. Spinal Cord 39:193–203

    Article  CAS  PubMed  Google Scholar 

  • Matsuda NM, Miller SM, Evora PRB (2009) The chronic gastrointestinal manifestations of Chagas disease. Clinics 64:1219–1224

    Article  PubMed  PubMed Central  Google Scholar 

  • Miller AS, Furness JB, Costa M (1989) The relationship between gastrin cells and bombesin-like immunoreactive nerve fibres in the gastric antral mucosa of guinea-pig, rat, dog and man. Cell Tissue Res 257:171–178

    Article  CAS  PubMed  Google Scholar 

  • Neuhuber WL, Kressel M, Stark A, Berthoud HR (1998) Vagal efferent and afferent innervation of the rat esophagus as demonstrated by anterograde DiI and DiA tracing: focus on myenteric ganglia. J Auton Nerv Syst 70:92–102

    Article  CAS  PubMed  Google Scholar 

  • Neuhuber WL, Raab M, Berthoud H-R, Wörl J (2006) Innervation of the mammalian esophagus. Adv Anat Embryol Cell Biol 185:1–73

    Article  PubMed  Google Scholar 

  • Norlén P, Ericsson P, Kitano M, Ekelund M, Håkanson R (2005) The vagus regulates histamine mobilization from rat stomach ECL cells by controlling their sensitivity to gastrin. J Physiol 564:895–905

    Article  PubMed  PubMed Central  Google Scholar 

  • Podewils LJ, Mintz ED, Nataro JP, Parashar UD (2004) Acute, infectious diarrhea among children in developing countries. Semin Pediatr Infect Dis 15:155–168

    Article  PubMed  Google Scholar 

  • Rindi G, Ratineau C, Ronco A, Candusso ME, Tsai M, Leiter AB (1999) Targeted ablation of secretin-producing cells in transgenic mice reveals a common differentiation pathway with multiple enteroendocrine cell lineages in the small intestine. Development 126:4149–4156

    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 

  • Rowland KJ, Brubaker PL (2011) The “cryptic” mechanism of action of glucagon-like peptide-2. Am J Physiol 301:G1–G8

    Article  CAS  Google Scholar 

  • Russell-Jones D, Cuddihy RM, Hanefeld M et al (2012) Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (Duration-4). Diabetes Care 35:252–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sandoval D, Dunki-Jacobs A, Sorrell J, Seeley RJ, D'Alessio DD (2013) Impact of intestinal electrical stimulation on nutrient-induced GLP-1 secretion in vivo. Neurogastroenterol Motil 25:700–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Savidge TC, Newman P, Pothoulakis C et al (2007) Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. Gastroenterology 132:1344–1358

    Article  CAS  PubMed  Google Scholar 

  • Schubert ML, Peura DA (2008) Control of gastric acid secretion in health and disease. Gastroenterology 134:1842–1860

    Article  CAS  PubMed  Google Scholar 

  • Seymour NE, Andersen DK (1999) Surgery for peptic ulcer disease and postgastrectomy syndromes. In: Yamada T, Alpers DH, Laine L, Owyang C, Powell DW (eds) Textbook of gastroenterology, 3rd edn. Lippincott Williams & Wilkins, Philadelphia, PA, pp 1530–1548

    Google Scholar 

  • Shirazi-Beechey SP, Moran AW, Batchelor DJ, Daly K, Al-Rammahi M (2011) Influences of food constituents on gut health glucose sensing and signalling; regulation of intestinal glucose transport. Proc Nutr Soc 70:185–193

    Article  CAS  PubMed  Google Scholar 

  • Sigalet DL, Wallace LE, Holst JJ, Martin GR, Kaji T, Tanaka H, Sharkey KA (2007) Enteric neural pathways mediate the anti-inflammatory actions of glucagon-like peptide 2. Am J Physiol 293:G211–G221

    Article  CAS  Google Scholar 

  • Sjövall H, Abrahamsson H, Westlander G, Gillberg R, Redfors S, Jodal M, Lundgren O (1986) Intestinal fluid and electrolyte transport in man during reduced circulating blood volume. Gut 27:913–918

    Article  PubMed  PubMed Central  Google Scholar 

  • Sjövall M, Ekblad E, Lundell L, Sundler F (1990) Gastrin-releasing peptide: neuronal distribution and spatial relation to endocrine cells in the human upper gut. Regul Pept 28:47–55

    Article  PubMed  Google Scholar 

  • Stengel A, Goebel M, Wang L, Taché Y (2010a) Ghrelin, des-acyl ghrelin and nesfatin-1 in gastric X/A-like cells: role as regulators of food intake and body weight. Peptides 31:357–369

    Article  CAS  PubMed  Google Scholar 

  • Stengel A, Goebel M, Wang L, Taché Y, Sachs G, Lambrecht NWG (2010b) Differential distribution of ghrelin-O-acyltransferase (GOAT) immunoreactive cells in the mouse and rat gastric oxyntic mucosa. Biochem Biophys Res Commun 392:67–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swenson O (2002) Hirschsprung’s disease: a review. Pediatrics 109:914–918

    Article  PubMed  Google Scholar 

  • Sykaras AG, Demenis C, Cheng L, Pisitkun T, Mclaughlin JT, Fenton RA, Smith CP (2014) Duodenal CCK cells from male mice express multiple hormones including ghrelin. Endocrinology 155:3339–3351

    Article  PubMed  Google Scholar 

  • Szecowka J, Tatemoto K, Rajamaki G, Efendic S (1983) Effects of PYY and PP on endocrine pancreas. Acta Physiol Scand 119:123–126

    Article  CAS  PubMed  Google Scholar 

  • Thomas C, Gioiello A, Noriega L et al (2009) TGR5-Mediated bile acid sensing controls glucose homeostasis. Cell Metab 10:167–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toumi F, Neunlist M, Cassagnau E, Parois S, Laboisse CL, Galmiche J-P, Jarry A (2003) Human submucosal neurones regulate intestinal epithelial cell proliferation: evidence from a novel co-culture model. Neurogastroenterol Motil 15:239–242

    Article  CAS  PubMed  Google Scholar 

  • Weigert N, Li YY, Schick RR, Coy DH, Classen M, Schusdziarra V (1997) Role of vagal fibers and bombesin/gastrin-releasing peptide-neurons in distension-induced gastrin release in rats. Regul Pept 69:33–40

    Article  CAS  PubMed  Google Scholar 

  • Widerström-Noga EG, Felipe-Cuervo E, Broton JG, Duncan RC, Yezierski RP (1999) Perceived difficulty in dealing with consequences of spinal cord injury. Arch Phys Med Rehabil 80:580–586

    Article  PubMed  Google Scholar 

  • Wright EM, Loo DDF (2000) Coupling between Na+, sugar, and water transport across the intestine. Ann N Y Acad Sci 915:54–66

    Article  CAS  PubMed  Google Scholar 

  • Wu M, Majewski M, Wojtkiewicz J, Vanderwinden J-M, Adriaensen D, Timmermans J-P (2003) Anatomical and neurochemical features of the extrinsic and intrinsic innervation of the striated muscle in the porcine esophagus: evidence for regional and species differences. Cell Tissue Res 311:289–297

    CAS  PubMed  Google Scholar 

  • Young RL (2011) Sensing via intestinal sweet taste pathways. Front Neurosci 5:1–13

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Neuroscience, University of Melbourne and Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3010, Australia

    John B. Furness

Authors
  1. John B. Furness
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John B. Furness .

Editor information

Editors and Affiliations

  1. Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia

    Stuart Brierley

  2. Department of Human Physiology, School of Medicine, Flinders University,, Adelaide, South Australia, Australia

    Marcello Costa

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Furness, J.B. (2016). Integrated Neural and Endocrine Control of Gastrointestinal Function. In: Brierley, S., Costa, M. (eds) The Enteric Nervous System. Advances in Experimental Medicine and Biology(), vol 891. Springer, Cham. https://doi.org/10.1007/978-3-319-27592-5_16

Download citation

Publish with us

Policies and ethics

Search

Navigation