Colon pp 187-209 | Cite as

Nerves of the Colon

  • Mats Jodal
  • Ove Lundgren
Part of the Topics in Gastroenterology book series (TGEN)


The colon contains a nervous system of its own, consisting of the different nerve plexuses in the wall. Langley1 once proposed that the plexuses throughout the gastrointestinal tract should be considered a special part of the autonomic system, the “enteric nervous system.” This abandoned view was in part based on the incorrect notion that there are no nervous connections between the plexuses and the central nervous system. However, overwhelming experimental support now exists for the view that the intestinal plexuses can induce complex, specialized physiological adjustments, such as peristaltic movements, in the absence of any central connections. Furthermore, recent histochemical investigations have produced evidence for the possible involvement of a large number of neurotransmitters, mainly peptides, in the neurons of the intestinal wall, adding to the complexity. Thus, the time may be ripe to revive Langley’s concept of an enteric nervous system.


Vasoactive Intestinal Polypeptide Enteric Nervous System Myenteric Plexus Myenteric Neuron Peptidergic Neuron 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Langley JN: The Autonomic Nervous System. Cambridge, W Hefner & Sons Ltd, part I, 1921.Google Scholar
  2. 2.
    Gabella G: Innervation of the gastrointestinal tract. Int Rev Cytol 59:129–193, 1979.PubMedCrossRefGoogle Scholar
  3. 3.
    Gabella G: Structure of the autonomic nervous system. New York, John Wiley & Sons Inc, 1976.CrossRefGoogle Scholar
  4. 4.
    Schofield GC: Anatomy of muscular and neural tissues in the alimentary canal, in Code CF (ed): Handbook of Physiology. Section 6: Alimentary Canal, Vol 4. Washington, DC, American Physiological Society, 1968, pp 1579–1627.Google Scholar
  5. 5.
    Hultén L: Extrinsic nervous control of colonic motility and blood flow. Acta Physiol Scand suppl 335, 1–116, 1969.Google Scholar
  6. 6.
    Hökfelt T, Johansson O, Ljungdahl A, et al: Peptidergic neurons. Nature 284:515–521, 1980.PubMedCrossRefGoogle Scholar
  7. 7.
    Hökfelt T, Elfvin LV, Elde R, et al: Occurrence of somatostatin-like immunoreactivity in some peripheral sympathetic noradrenergic neurons. Proc Natl Acad Sci USA 74:3587–3591, 1977.PubMedCrossRefGoogle Scholar
  8. 8.
    Hökfelt T, Elfvin LG, Schultzberg M, et al: Immunohistochemical evidence of vasoactive intestinal polypeptide-containing neurons and nerve fibers in sympathetic ganglia. Neuroscience 2:885–896, 1977.CrossRefGoogle Scholar
  9. 9.
    Hökfelt T, Elfvin LG, Schultzberg M, et al: On the occurrence of substance P-containing fibers in sympathetic ganglia: Immunohistochemical evidence. Brain Res 132:29–41, 1977.PubMedCrossRefGoogle Scholar
  10. 10.
    Hökfelt T, Johansson O, Ljungdahl A, et al: Histochemistry of transmitter interactions: Neuronal coupling and coexistence of transmitter. Adv Pharmacol Ther 2:131–143, 1979.Google Scholar
  11. 11.
    Burnstock G, Hökfelt T, Gershon MD, et al: Non-adrenergic, non-cholinergic autonomic neurotransmission mechanisms. Neurosci Res Prog Bull 17:379–519, 1979.Google Scholar
  12. 12.
    Lundberg JM, Hökfelt T, Nilsson G, et al: Peptide neurons in the vagus, splanchnic and sciatic nerves. Acta Physiol Scand 104:499–501, 1978.PubMedCrossRefGoogle Scholar
  13. 13.
    Lundberg JM, Hö;kfelt T, Kewenter J, et al: Substance P, VIP, and enkephalin-like immunoreactivity in the human vagus nerve. Gastroenterology 77:468–471, 1979.PubMedGoogle Scholar
  14. 14.
    Furness JB, Costa M: Types of nerves in the enteric nervous system. Neuroscience 5:1–20, 1980.PubMedCrossRefGoogle Scholar
  15. 15.
    Cook RD, Burnstock G: The ultrastructure of Auerbach’s plexus in the guinea-pig. I. Neuronal elements. J Neurocytol 5:171–194, 1976.PubMedCrossRefGoogle Scholar
  16. 16.
    Gunn M: Histological and histochemical observations on the myentric and submucous plexuses of mammals. J Anat 102:223–239, 1968.PubMedGoogle Scholar
  17. 17.
    Burnstock G: Autonomic innervation and transmission. Br Med Bull 35:255–262, 1979.PubMedGoogle Scholar
  18. 18.
    Norberg KA, Hamberger B: The sympathetic adrenergic neuron. Acta Physiol Scand 63suppl 238:1–2, 1964.Google Scholar
  19. 19.
    Dogiel AS: Zur Frage über die Ganglien der Darmgeflechte bei den Säugetieren. Anat Anz 10:517–528, 1895.Google Scholar
  20. 20.
    Dogiel, AS: Über den Bau der Ganglien in den Geflechten des Darmes und der Gallenblase des Menschen und der Säugetiere. Arch Anat Physiol Physiol Abt 130–158, 1899.Google Scholar
  21. 21.
    Baumgarten HG, Holstein AF, Owman Ch: Auerbach’s plexus of mammals and man: Electron microscopic identification of three different types of neuronal processes from Rhesus monkeys, guinea pigs and man. Z. Zellforsch Mikrosk Anat 106:376–397, 1970.PubMedCrossRefGoogle Scholar
  22. 22.
    Palay SL, Chan-Palay V: A guide to the synaptic analysis of the neuropil. Symp Quant Biol 40:1–16, 1975.CrossRefGoogle Scholar
  23. 23.
    Burnstock G: Purinergic nerves. Pharmacol Rev 24:509–581, 1972.PubMedGoogle Scholar
  24. 24.
    Larsson LI: Ultrastructural localization of a new neuronal peptide (VIP). Histochemistry 54:173–176, 1977.PubMedCrossRefGoogle Scholar
  25. 25.
    Dreyfus CF, Sherma DL, Gershon MD: Uptake of serotonin by intrinsic neurons of the myenteric plexus grown in organotypic tissue culture. Brain Res 128:109–123, 1977.PubMedCrossRefGoogle Scholar
  26. 26.
    Rothman TP, Ross LL, Gershon MD: Separately developing axonal uptake of 5-hydroxytryptamine and norepinephrine in the fetal ileum of the rabbit. Brain Res 115:437–456, 1976.PubMedCrossRefGoogle Scholar
  27. 27.
    Furness JB, Costa M: The adrenergic innervation of the gastrointestinal tract Rev Physiol 69:1–51, 1974.Google Scholar
  28. 28.
    Furness JB, Costa M: Morphology and distribution of intrinsic adrenergic neurones in the proximal colon of the guinea-pig. Z Zellforsch Mikrosk Anat 120:346–363, 1971.CrossRefGoogle Scholar
  29. 29.
    Burnstock G, Costa M: Adrenergic Neurons. New York, John Wiley & Sons Inc, 1975.Google Scholar
  30. 30.
    Ahlman H, Enerbäck L: A cytofluorometric study of the myenteric plexus in the guinea-pig. Cell Tissue Res 153:419–434, 1974.PubMedCrossRefGoogle Scholar
  31. 31.
    Ahlman H, Enerback L, Kewenter J, et al: Effects of extrinsic denervation on the fluorescences of monoamines in the small intestine of the cat. Acta Physiol Scand (suppl) 401:1–31, 1973.Google Scholar
  32. 32.
    Alumets J, Håkanson R, Sundler F, et al: Leu-enkephalin-like material in nerves and enterochromaffin cells in the gut. Histochemistry 56:187–196, 1978.PubMedCrossRefGoogle Scholar
  33. 33.
    Kosterlitz HW, Lydon RJ, Watt AJ: The effects of adrenaline, noradrenaline and isoprenaline on inhibitory α and β adrenoceptors in the longitudinal muscle of the guinea-pig ileum. Br J Pharmacol 39:398–413, 1970.PubMedCrossRefGoogle Scholar
  34. 34.
    Feldberg W, Lin RCY: Synthesis of acetylcholine in the wall of the digestive tract. J Physiol (London) 111:96–118, 1950.Google Scholar
  35. 35.
    Filogamo G, Marchisio PC: Choline acetyltranserase activity of rabbit ileum wall. The effects of extrinsic and intrinsic denervation and of combined experimental hypertrophy. Arch Int Physiol Biochim 78:141–152, 1970.PubMedCrossRefGoogle Scholar
  36. 36.
    Norberg KA: Adrenergic innervation of the intestinal wall studied by fluorescence microscopy. Int J Neuropharmacol 3:379–382, 1964.PubMedCrossRefGoogle Scholar
  37. 37.
    Read JB, Burnstock G: Comparative histochemical studies of adrenergic nerves in the enteric plexuses of vertebrate large intestine. Comp Biochem Physiol 27:505–517, 1968.PubMedCrossRefGoogle Scholar
  38. 38.
    Cooper JR, Bloom FE, Roth RH: The Biochemical Basis of Neuropharmacology New York, Oxford University Press, 1978.Google Scholar
  39. 39.
    Gershon MD: Biochemistry and physiology of serotonergic transmission, in Brookhart JM (ed): Handbook of Physiology. Section 1: The Nervous System. Bethesda, Md, American Physiological Society, pp 573–623, 1977.Google Scholar
  40. 40.
    Costa M, Furness JB: On the possibility that an indoleamine is a neurotransmitter in the gastrointestinal tract. Biochem Pharmacol 28:565–571, 1979.PubMedCrossRefGoogle Scholar
  41. 41.
    Ålund M, Olson L: Quinacrine-binding nervous elements in intraocular grafts of intestinal smooth muscle tissue. Med Biol 58:45–48, 1980.PubMedGoogle Scholar
  42. 42.
    Olson L, Ålund M, Norberg KA: Fluorescense-microscopical demonstration of a population of gastrointestinal nerve fibres with a selective affinity for quinacrine. Cell Tissue Res 171:407–423, 1976.PubMedCrossRefGoogle Scholar
  43. 43.
    Ålund M: Quinacrine histofluorescence: On the affinity to nervous and endocrine elements of an acrid-ine derivative. Stockholm, Tryckeri Balder AB, 1980.Google Scholar
  44. 44.
    Costa M, Cuello AC, Furness JB et al: Distribution of enteric neurons showing immunoreactivity for substance P in the guinea-pig ileum. Neuroscience 5:323–331, 1980.PubMedCrossRefGoogle Scholar
  45. 45.
    Nilsson G, Larsson LI, Hakanson R, et al: Localization of substance P-like immunoreactivity in mouse gut. Histochemistry 43:97–99, 1975.PubMedCrossRefGoogle Scholar
  46. 46.
    Pearse, AGE, Polak JM: Immunocytochemical localization of substance P in mammalian intestine. Histochemistry 41:373–375, 1975.PubMedCrossRefGoogle Scholar
  47. 47.
    Schultzberg M, Hökfelt T, Nilsson G, et al.: Distribution of peptide and catecholamine-containing neurons in the gastrointestinal tract of rat and guinea-pig: Immunohistochemical studies with antisera to substance P, vasoactive intestinal polypeptide, enkephalins, somatostatin, gastrin, cholecystokinin, neurotensin and dopamine ß-hydroxylase. Neuroscience 5:689–744, 1980.PubMedCrossRefGoogle Scholar
  48. 48.
    Sundler F, Håkanson R, Larsson LI, et al: Substance P in the gut: An immunochemical and immunohistochemical study of its distribution and development, in von Euler US, Pernow B (eds); Substance P. New York, Raven Press, pp 59–65, 1977.Google Scholar
  49. 49.
    Franco R, Costa M, Furness JB: Evidence for the release of endogenous substance P from intestinal nerves. Naunyn-Schmiedebergs Arch Pharmacol 306:195–201, 1979.CrossRefGoogle Scholar
  50. 50.
    Franco R, Costa M, Furness JB: Evidence that axons containing substance P in the guinea-pig ileum are of intrinsic origin Naunyn-Schmiedeberg–s Arch Pharmacol 307:57–63, 1979.CrossRefGoogle Scholar
  51. 51.
    Katayama Y, North RA: Does substance P mediate slow synaptic excitation within the myenteric plexus? Nature (London) 274:387–388, 1978.CrossRefGoogle Scholar
  52. 52.
    Polak JM, Pearse AGE, Garaud JC, et al: Cellular localization of a vasoactive intestinal peptide in the mammalian and avian gastrointestinal tract. Gut 15:720–724, 1974.PubMedCrossRefGoogle Scholar
  53. 53.
    Bryant MG, Polak JM, Modlin IM, et al: Possible dual role for vasoactive intestinal peptide as gastrointestinal hormone and neurotransmitter substance. Lancet 1:991–993, 1976.PubMedCrossRefGoogle Scholar
  54. 54.
    Costa M, Furness JB, Buffa R, et al: Distribution of enteric nerve cell bodies and axons showing immunoreactivity for vasoactive intestinal polypeptide in the guinea-pig intestine. Neuroscience 5:587–596, 1980.PubMedCrossRefGoogle Scholar
  55. 55.
    Fuxe K, Hökfelt T, Said SI, et al: Vasoactive intestinal polypeptide and the nervous system: Immunohistochemical evidence for localization in central and peripheral neurons, particularly intracortical neurons of the cerebral cortex. Neurosci Lett 5:241–246, 1977.PubMedCrossRefGoogle Scholar
  56. 56.
    Larsson LI, Fahrenkrug J, Schaffalitzky de Muckadell O, et al: Localization of vasoactive intestinal polypeptide (VIP) to central and peripheral neurons. Proc Natl Acad Sci USA 73:3197–3200, 1976.PubMedCrossRefGoogle Scholar
  57. 57.
    Fahrenkrug J, Haglund U, Jodal M, et al: Nervous release of vasoactive intestinal polypeptide in the gastrointestinal tract of cats: Possible Physiological implications. J Physiol 284:291–305, 1978.PubMedGoogle Scholar
  58. 58.
    Hughes J: Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Res 88:295–308, 1975.PubMedCrossRefGoogle Scholar
  59. 59.
    Linnoila RI, DiAugustine RP, Miller RJ, et al: An immunohistochemical and radioimmunological study of the distribution of Met5 and Leu5-enkephalin in the gastrointestinal tract. Neuroscience 3:1187–1196, 1978.PubMedCrossRefGoogle Scholar
  60. 60.
    Elde R, Hökfelt T, Johansson O, et al: Immunohistochemical studies using antibodies to leucine-enkephalin: Initial observations on the nervous system of the rat. Neuroscience 1:349–351, 1976.PubMedCrossRefGoogle Scholar
  61. 61.
    Polak JM, Sullivan SN, Bloom SR, et al: Enkephalin-like immunoreactivity in the human gastrointestinal tract. Lancet 1:972–974, 1977.PubMedCrossRefGoogle Scholar
  62. 62.
    Schultzberg M, Hökfelt T, Terenius L, et al: Enkephalin immunoreactive nerve fibers and cell bodies in sympathetic ganglia of the guinea-pig and rat. Neuroscience 4:249–270, 1979.PubMedCrossRefGoogle Scholar
  63. 63.
    Larsson LI, Childers S, Snyder SH: Met- and Leu-enkephalin immunoreactivity in separate neurones. Nature London 282:407–410, 1979.PubMedCrossRefGoogle Scholar
  64. 64.
    Schulz R, Wuster M, Simantov R, et al: Electrically stimulated release of opiate-like material from the myenteric plexus of the guinea pig ileum. Eur J Pharmacol 41:347–348, 1977.PubMedCrossRefGoogle Scholar
  65. 65.
    van Nueten JM, van Ree JM, Vanhoutte PM: Inhibition by met-enkephalin of peristaltic activity in the guinea pig ileum, and its reversal by naloxone. Eur J Pharmacol 41:341–342, 1977.PubMedCrossRefGoogle Scholar
  66. 66.
    Waterfield AA, Smokcum RWJ, Hughes J, et al: In vitro pharmacology of the opioid peptides, enkephalins and endorphins. Eur J Pharmacol 43:107–116, 1977.PubMedCrossRefGoogle Scholar
  67. 67.
    Costa M, Patel Y, Furness JB, et al: Evidence that some intrinsic neurons of the intestine contain somatostatin. Neurosci Lett 6:215–222, 1977.PubMedCrossRefGoogle Scholar
  68. 68.
    Hökfelt T, Johansson O, Efendic S et al: Are there somatostatin-containing nerves in the rat gut? Immunohistochemical evidence for a new type of peripheral nerves. Experientia 31:852–854, 1975.PubMedCrossRefGoogle Scholar
  69. 69.
    Furness JB, Costa M: Actions of somatostatin on exictatory and inhibitory nerves in the intestine. Eur J Pharmacol 56:69–74, 1979.PubMedCrossRefGoogle Scholar
  70. 70.
    Guillemin R: Somatostatin inhibits the release of acetylcholine induced electrically in the myenteric plexus. Endocrinology 99:1653–1654, 1976.PubMedCrossRefGoogle Scholar
  71. 71.
    Lundberg JM, Hökfelt T, Schultzberg M, et al: Occurrence of vasoactive intestinal polypeptide (VIP)-like immunoreactivity in certain cholinergic neurons of the cat: Evidence from combined immunohistochemistry and acetylcholinesterase staining. Neuroscience 4:1539–1559, 1979.PubMedCrossRefGoogle Scholar
  72. 72.
    Hultên L, Jodal M, Lundgren O: Extrinsic nervous control of colonic blood flow. Acta Physiol Scand, Suppl 335, 39–49, 1969.Google Scholar
  73. 73.
    Wood JD: Neurophysiology of Auerbach’s plexus and control of intestinal motility. Physiol Rev 55:307–324, 1975.PubMedGoogle Scholar
  74. 74.
    Hirst GDS, Holman ME, Spence I: Two types of neurons in the myenteric plexus of duodenum in the guinea-pig. J Physiol 263:303–326, 1974.Google Scholar
  75. 75.
    Nishi S, North RA: Intracellular recording from the myenteric plexus of the guinea-pig ileum. J Physiol 231:471–491, 1973.PubMedGoogle Scholar
  76. 76.
    Hirst GDS: Mechanisms of peristalsis Br Med Bull 35:263–268, 1979.Google Scholar
  77. 77.
    Wood JD, Mayer CJ: Intracellular study of tonic-type enteric neurons in guinea pig small intestine. J Neurophysiol 42:569–581, 1979.PubMedGoogle Scholar
  78. 78.
    Grafe P, Mayer CJ, Wood JD: Evidence that substance P does not mediate slow synaptic excitation within the myenteric plexus. Nature (London) 279:720–721, 1979.CrossRefGoogle Scholar
  79. 79.
    Wood JD, Mayer CJ: Slow synaptic excitation mediated by serotonin in Auerbach’s plexus. Nature London 276:836–837, 1978.PubMedCrossRefGoogle Scholar
  80. 80.
    Wood JD, Mayer CJ: Serotonergic activation of tonic-type enteric neurons in guinea pig small bowel. J Neurophysiol 42:582–593, 1979.PubMedGoogle Scholar
  81. 81.
    Williams JT, North RA: Vasoactive intestinal polypeptide excites neurons of the myenteric plexus. Brain Res 175:174–177, 1979.PubMedCrossRefGoogle Scholar
  82. 82.
    North RA, Katayama Y, Williams JT: On the mechanisms and site of action of enkephalin on single myenteric neurons. Brain Res 165:67–77, 1979.PubMedCrossRefGoogle Scholar
  83. 83.
    Biber B, Lundgren O, Svanvik J: Studies on the intestinal vasodilatation observed after mechanical stimulation of the mucosa of the gut. Acta Physiol Scand 82:177–190, 1971.PubMedCrossRefGoogle Scholar
  84. 84.
    Fasth S, Hulten L, Lundgren O, et al: Vascular responses to mechanical stimulation of the mucosa of the cat colon. Acta Physiol Scand 101:98–104, 1977.PubMedCrossRefGoogle Scholar
  85. 85.
    Ohkubo K: Studien über das intramural Nervensystem des Verdauungskanals. Part II. Japan J Med Sci 6:21ü37, 1936.Google Scholar
  86. 86.
    Irwin DA: The anatomy of the Auerbach’s plexus. Am J Anat 49:141–166, 1931.CrossRefGoogle Scholar
  87. 87.
    Matsuo H: A contribution on the anatomy of Auerbach’s plexus. Jap J Med Sci Anat 4:417–428, 1934.Google Scholar
  88. 88.
    Ohkubo K: Studien über das intramural Nervensystem des Verdauungskanals. Part III. Jap J Med Sci 6:219–247, 1936.Google Scholar
  89. 89.
    Tafuri WL: Auerbach’s plexus in guinea pig. I. A quantitative study of the ganglia and nerve cells in the ileum, caecum and colon. Acta Anat 31:522–530, 1957.PubMedCrossRefGoogle Scholar
  90. 90.
    Ohkubo K: Studies on the intrinsic nervous system of the digestive tract. I. The submucous plexus of guinea pig. Japan J Med Sci 6:1–20, 1936.Google Scholar
  91. 91.
    Tafuri WL, de Alemida Campos F: Der Auerbachsche Plexus bei der Maus. Z Naturforsch 13b:816–819, 1958.Google Scholar
  92. 92.
    Fuxe K. Hökfelt T: Histochemical fluorescence detection of changes in central monamine neurones proved by drugs acting on the CNS. Triangle 10:73, 1971.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1983

Authors and Affiliations

  • Mats Jodal
    • 1
  • Ove Lundgren
    • 1
  1. 1.Department of PhysiologyUniversity of GöteborgGöteborgSweden

Personalised recommendations