Serotonin: Its Role and Receptors in Enteric Neurotransmission

  • M. D. Gershon
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 294)


The gastrointestinal tract represents the largest depot of 5-hydroxytryptamine (5-HT) in the body (Erspamer, 1966). Within the gut, 5-HT is found both in enteroendocrine (EC) cells in the epithelium of the mucosa (Erspamer, 1966; Nilsson et al., 1985) and in neurons of the myenteric plexus (Costa et al., 1982; Gershon, 1982; Furness and Costa, 1987). The 5-HT-containing EC cells develop from embryonic endoderm, while the neurons develop from the neural crest (Le Douarin, 1982). Neither the roles played in gastrointestinal physiology by EC cell 5-HT nor those of serotonergic neurons have been ascertained; however, 5-HT is probably involved in the regulation of gastrointestinal motility. A variety of stimuli have been reported to release 5-HT from EC cells, including mucosal pressure (Bülbring and Lin, 1958; Bülbring and Crema, 1959) and activation of splanchnic or vagus nerves (Ahlman et al., 1976; Ahlman and Dahlström, 1983; Gronstad et al., 1985). Pressure applied to the mucosa of the gut also initiates the peristaltic reflex, a response that can also be elicited by mucosal but not serosal application of 5-HT (Bülbring and Crema, 1958; Bülbring and Lin, 1958). It has thus been proposed that EC cells are pressure receptors and that they release 5-HT, not into the lumen of the bowel, but to the lamina propria, where intrinsic primary afferent nerve fibers that are sensitive to 5-HT are located. If this hypothesis is correct, then enteric neuronal 5-HT receptors would have to be present in the lamina propria. Enteric serotonergic neurons are interneurons, innervating serotonergic and other ganglion cells in both enteric plexuses (Dreyfus et al., 1977; Furness and Costa, 1982, 1987; Gershon and Sherman, 1987). Enteric neuronal 5-HT receptors, therefore, should also be found with enteric ganglia.


Lamina Propria Enteric Nervous System Myenteric Plexus Enteric Neuron Myenteric Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ahlman, H., and Dahlström, A., 1983, Vagal mechanisms controlling serotonin release from the gastrointestinal tract and pyloric motorfunction, J. Auton. Nerv. Syst., 9: 119–140.PubMedCrossRefGoogle Scholar
  2. Ahlman, H., Lundberg, J., Dahlström, A., and Kewenter, J., 1976, A possible vagal adrenergic release of serotonin from enterochromaffin cells in the cat, Acta Physiol. Scand., 98: 366–375.PubMedCrossRefGoogle Scholar
  3. Bornstein, J., North, R.A., Costa, M., and Furness, J.B., 1984, Excitatory synaptic potentials due to activation of neurons with short projection in the myenteric plexus, Neuroscience, 11: 723–731.PubMedCrossRefGoogle Scholar
  4. Boyd, H., Burnstock, G., Campbell, G., Jowett, A., O’Shea, J., and Wood, M., 1963, The cholinergic blocking action of adrenergic blocking agents in pharmacological analysis of autonomic innervation, Br. J. Pharmacol. Chemother., 20: 418–435.PubMedGoogle Scholar
  5. Branchek, T.A., and Gershon, M.D., 1987, Development of neural receptors for serotonin in the murine bowel, J. Comp. Neurol., 258: 597–610.PubMedCrossRefGoogle Scholar
  6. Branchek, T.A., Kates, M., and Gershon, M.D., 1984b, Enteric receptors for 5-hydroxytryptamine, Brain Res., 324: 107–118.PubMedCrossRefGoogle Scholar
  7. Branchek, T., Mawe, G., and Gershon, M.D., 1988a, Characterization and localization of a peripheral neural 5-hydroxytryptamine receptor subtype with a selective agonist, 3H-5-hydroxyindalpine, J. Neurosci., 8: 2582–2595.PubMedGoogle Scholar
  8. Branchek, T., Mawe, G., and Gershon, M.D., 1988b, Actions of BRL 24924 on enteric neurons: Role of 5-HT1P receptors, Proc. Symp. Cardiovascular Pharmacology of Serotonin, Amsterdam, The Netherlands.Google Scholar
  9. Branchek, T., Rothman, T., and Gershon, M.D., 1984a, Serotonin receptors on the processes of intrinsic enteric neurons: Reduction in the aganglionic bowel of the ls/ls mouse, Soc. Neurosci. Abstr., 10: 1097.Google Scholar
  10. Brownlee, G., and Johnson, E.S., 1963, The site of the 5-hydroxytryptamine receptor on the peristaltic reflex, Br. J. Pharmacol., 21: 306–322.Google Scholar
  11. Bülbring, E., and Crema, A., 1958, Observations concerning the action of 5-hydroxytryptamine on the peristaltic reflex, Br. J. Pharmacol., 13: 444–457.Google Scholar
  12. Bülbring, E., and Crema, A., 1959, The release of 5-hydroxytryptamine in relation to pressure exerted on the intestinal mucosa, J. Physiol. (London), 146: 381–407.Google Scholar
  13. Bülbring, E., and Gershon, M.D., 1967, 5-Hydroxytryptamine participation in the vagal inhibitory innervation of the stomach, J. Physiol. (London), 192: 823–846.Google Scholar
  14. Bülbring, E., and Lin, R.C.Y., 1958, The effect of intraluminal application of 5-hydroxytryptamine and 5-hydroxytryptophan on peristalsis, the local production of 5-hydroxytryptamine and its release in relation to intraluminal pressure and propulsive activity, J. Physiol. (London), 140: 381–407.Google Scholar
  15. Cassuto, J., Jodal, M., Tuttle, R., and Lundgren, O., 1982, 5-Hydroxytryptamine and cholera secretion, Scand. J. Gastroenterol., 17: 695–703.PubMedCrossRefGoogle Scholar
  16. Cooke, H.J., 1987, Neural and humoral regulation of small intestinal electrolyte transport, in: “Physiology of the Gastrointestinal Tract”, Vol. 2, Johnson, L.R., ed., Raven Press, New York, pp. 1307–1350.Google Scholar
  17. Cooke, H.J., and Carey, H.V., 1985, Pharmacological analysis of 5-hydroxytryptamine actions on guinea pig ileal mucosa, Eur. J. Pharmacol., 111: 329–337.PubMedCrossRefGoogle Scholar
  18. Costa, M., and Furness, J.B., 1976, The peristaltic reflex: an analysis of the nerve pathways and their pharmacology, Naunyn-Schmiedeberg’s Arch. Pharmacol., 294: 47–60.CrossRefGoogle Scholar
  19. Costa, M., and Furness, J.B., 1979, The sites of action of 5-HT in nerve muscle preparations from guinea-pig small intestine and colon, Br. J. Pharmacol., 65: 237–248.PubMedGoogle Scholar
  20. Costa, M., Furness, J.B., Cuello, A.C., Verhofstad, A.A.J., Steinbusch, H.W.J., and Eide, R.P., 1982, Neurons with 5-hydroxytryptamine-like immunoreactivity in the enteric nervous system: their visualization and reactions to drug treatment, Neuroscience, 7: 351–363.PubMedCrossRefGoogle Scholar
  21. Davidson, H.I., and Pilot, M.A., 1986, Does endogenous neuronal 5-hydroxytryptamine influence canine intestinal motility, J. Physiol. (London), 376:49P.Google Scholar
  22. Day, M., and Vane, J.R., 1963, An analysis of the direct and indirect actions of drugs on the isolated guinea-pig ileum, Br. J. Pharmacol. Chemother., 20: 150–170.PubMedGoogle Scholar
  23. Dingeldine, R., and Goldstein, A., 1976, Effect of synaptic transmission blockade on morphine action in the guinea pig myenteric plexus, J. Pharmacol. Exp. Ther., 196: 97–106.Google Scholar
  24. Donowitz, M., Tai, Y.-H., and Asarkof, N., 1980, Effect of serotonin on active electrolyte transport in rabbit ileum, igall bladder, and colon, Amer. J. Physiol., 239: G463–G472.PubMedGoogle Scholar
  25. Drakontides, A.B., and Gershon, M.D., 1968, 5-HT receptors in the mouse duodenum, Br. J. Pharmacol., 33: 480–492.Google Scholar
  26. Dreyfus, C.F., Sherman, D., and Gershon, M.D., 1977, Uptake of serotonin by intrinsic neurons of the myenteric plexus grown in organotypic tissue culture, Brain Res., 128: 109–123.PubMedCrossRefGoogle Scholar
  27. Erde, S., Sherman, D., and Gershon, M.D., 1985, Morphology of the serotonergic innervation of physiologically identified cells of the guinea pig myenteric plexus, J. Neurosci., 5: 617–633.PubMedGoogle Scholar
  28. Erspamer, V., 1966, Occurrence of indolealkylamines in nature, in: “Handbook of Experimental Pharmacology, Vol. 19, 5-Hydroxytryptamine and Related Indolealkylamines”, Erspamer, V., ed., Springer, New York, pp. 132–181.Google Scholar
  29. Furness, J.B., and Costa, M., 1973, The nervous release and the action of substances which affect intestinal muscle through neither adrenoreceptors nor cholineroreceptors, Phil. Trans. Roy. Soc. Series, B265: 123–133.CrossRefGoogle Scholar
  30. Furness, J.B., and Costa, M., 1982, Neurons with 5-hydroxytryptamine-like immunoreactivity in the enteric nervous system: their projections in the guinea pig small intestine, Neuroscience, 7: 341–350.PubMedCrossRefGoogle Scholar
  31. Furness, J.B., and Costa, M., 1987, “The Enteric Nervous System”, Churchill, Livingston, New York, pp. 65–69.Google Scholar
  32. Gaddum, J.H., and Picarelli, Z.P., 1957, Two kinds of tryptamine receptor, Br. J. Pharmacol. Chemother., 12: 323–328.PubMedGoogle Scholar
  33. Galligan, J.J., Sukrprenant, A., Tonini, M., and North, R.A., 1988, Differential localization of 5-HT1 receptors on myenteric and submucosal neurons, Am. J. Physiol., (Gastrointest. Liver Physiol. 18), 255: G603–G611.PubMedGoogle Scholar
  34. Gershon, M.D., 1967, Effects of tetrodotoxin on innervated smooth muscle preparations, Br. J. Pharmacol., 29: 259–279.Google Scholar
  35. Gershon, M.D., 1982, Enteric serotonergic neurons, in: “Biology of Serotonergic Neurotransmission”, Osborne, N., ed., Wiley, New York, pp. 363–399.Google Scholar
  36. Gershon, M.D., Mawe, G., and Branchek, T., 1989, 5-Hydroxytryptamine and enteric neurons, in: “The Peripheral Actions of 5-HT”, Fozard, J.R., ed., Oxford Press, UK, pp. 247–264.Google Scholar
  37. Gershon, M.D., and Sherman, D.L. 1987, Noradrenergic innervation of serotonergic neurons in the myenteric plexus, J. Comp. Neurol., 259: 193–210.PubMedCrossRefGoogle Scholar
  38. Gershon, M.D., Takaki, M., Tamir, H., and Branchek, T., 1985, The enteric neural receptor for 5-hydroxytryptamine, Experientia, 41: 863–868.PubMedCrossRefGoogle Scholar
  39. Gronstad, K.O., DeMagistris, L., Dahlström, A., Nilsson, O., Price, B., Zinner, M.J., Jaffe, B.M., and Ahlman, H., 1985, The effects of vagal nerve stimulation on edoluminal release fo serotonin and substance P into the feline small intestine, Scand. J. Gastroenterol., 20: 163–169.PubMedCrossRefGoogle Scholar
  40. Hardcastle, J., Hardcastle, P.E.T., and Redfern, J.S., 1981, Action of 5-hydroxytryptamine on intestinal transport in the rat, J. Physiol. (London), 320: 41–55.Google Scholar
  41. Harry, J., 1963, The action of drugs on the circular muscle strip from the guinea pig isolated ileum, Br. J. Pharmacol. Chemother., 20: 399–417.PubMedGoogle Scholar
  42. Hirst, G.D.S., Holman, M.E., and Spence, I., 1974, Two types of neurons in the myenteric plexus of duodenum in the guinea pig, J. Physiol. (London), 236: 303–326.Google Scholar
  43. Holman, M.E., Hirst, G.D.S., and Spence, I., 1972, Preliminary studies of the neurons of Auerbach’s plexus using intracellular microelectrodes, Aust. J. Exp. Biol. Med., 50: 795–801.CrossRefGoogle Scholar
  44. Ireland, S.J., and Tyers, M.B., 1987, Pharmacological characterization of 5-hydroxytryptamine-induced depolarization of the rat isolated vagus nerve, Br. J. Pharmacol., 90: 229–238.PubMedGoogle Scholar
  45. Iversen, L.L., 1963, Uptake of noradrenalin by the isolated perfused rat heart, Br. J. Pharmacol. Chemother., 21: 523–537.PubMedGoogle Scholar
  46. Johnson, S.M., Katayama, Y., and North, R.A., 1980a, Multiple actions of 5-hydroxytryptamine on myenteric neurons of the guinea-pig ileum, J. Physiol. (London), 304: 459–479.Google Scholar
  47. Johnson, S.M., Katayama, Y., and North, R.A., 1980b, Slow synaptic potentials in neurons of the myenteric plexus, J. Physiol. (Lond.), 301: 505–516.Google Scholar
  48. Julé, Y., 1980, Nerve-mediated descending inhibition in the proximal colon of the rabbit, J. Physiol. (London), 159: 361–368.Google Scholar
  49. Kamikawa, Y., and Shimo, Y., 1983, Indirect action of 5-hydroxytryptamine on the isolated muscularis mucosa of the guinea pig oesophagus, Br. J. Pharmacol., 78: 103–110.PubMedGoogle Scholar
  50. Le Douarin, N.M., 1982, “The Neural Crest”, Cambridge, Cambridge University Press.Google Scholar
  51. Lew, W.Y.W., and Longhurst, J.C., 1986, Substance P, 5-hydroxytryptamine and bradykinin stimulate abdominal visceral afferents, Am. J. Physiol., 250: R465–R473.PubMedGoogle Scholar
  52. Mawe, G.M., Branchek, T., and Gershon, M.D., 1986, Peripheral neural serotonin receptors: Identifications and characterization with specific agonists and antagonists, Proc. Nat. Acad. Sci. USA, 83: 9799–9803.PubMedCrossRefGoogle Scholar
  53. Mawe, G.M., Branchek, T., and Gershon, M.D., 1988, Blockade of 5-HT-mediated enteric slow EPSPs by BRL 24924: Gastrokinetic effects, Am. J. Physiol., (Gastrointest. Liver Physiol.), in press.Google Scholar
  54. Nilsson, O., Ericson, L.E., Dahlström, A., Steinbusch, H.W.M., and Ahlman, H., 1985, Subcellular localization of serotonin immunoreactivity in rat enterochromaffin cells, Histochemistry, 82: 351–361.PubMedCrossRefGoogle Scholar
  55. Nishi, S., and North, R.A., 1973, Intracellular recording from the myenteric plexus of the guinea pig ileum, J. Physiol. (London), 231: 471–491.Google Scholar
  56. North, R.A., Henderson, C., Katayama, Y., and Johnson, S.M., 1980, Electrophysiological evidence of presynaptic inhibition of acetylcholine release by 5-hydroxytryptamine in the enteric nervous system, Neuroscience, 5: 581–586.PubMedCrossRefGoogle Scholar
  57. Ormsbee, H.S., Silver, D.A., and Hardy, F.E., 1984, Effects of 5-hydroxytryptamine on the migrating myoelectric complex in the canine intestine, J. Pharmacol. Exp. Ther., 231: 436–440.PubMedGoogle Scholar
  58. Paintal, A.S., 1964, Effects of drugs on vertebrae mechanoreceptors, Pharmacol. Rev., 16: 341–380.PubMedGoogle Scholar
  59. Paton, W.D.M., 1957, The action of morphine and related substances on contraction and on acetylcholine output on coaxially stimulated guinea-pig ileum, Br. J. Pharmacol. Chemother., 12: 119–127.PubMedGoogle Scholar
  60. Rattan, S., and Goyal, R.K., 1978, Evidence of 5-HT participation in vagal inhibitory pathway to opossum LES, Am. J. Physiol., 234: E273–E276.PubMedGoogle Scholar
  61. Sanger, G.J., 1985, Three different ways in which 5-hydroxytryptamine can affect choline activity in guinea-pig isolated ileum, J. Pharm. Pharmacol., 37: 584–586.PubMedCrossRefGoogle Scholar
  62. Schaumann, W., 1957, Inhibition by morphine of the release of acetylcholine from the intestine of the guinea pig, Br. J. Pharmacol., 12: 115–118.Google Scholar
  63. Schulz, R., and Cartwright, C., 1974, Effect of morphine on serotonin release from the myenteric plexus of the guinea pig, J. Pharmacol. Exp. Ther., 190: 420–430.PubMedGoogle Scholar
  64. Surprenant, A., and Crist, J., 1988, Electrophysiological characterization of functionally distinct 5-HT receptors on guinea-pig submucous plexus, Neuroscience, 24: 283–295.PubMedCrossRefGoogle Scholar
  65. Takaki, M., Branchek, T., Tamir, H., and Gershon, M.D., 1985a, Specific antagonism of enteric neural serotonin receptors by dipeptides of 5-hydroxytryptophan: evidence that serotonin is a mediator of slow synaptic excitation in the myenteric plexus, J. Neurosci., 5: 1769–1780.PubMedGoogle Scholar
  66. Takaki, M., Mawe, G.M., Barasch, J., and Gershon, M.D., 1985b, Physiological responses of guinea-pig myenteric neurons secondary to the release of endogenous serotonin by tryptamine, Neuroscience, 16: 223–240.PubMedCrossRefGoogle Scholar
  67. Vane, J.R., 1957, A sensitive method for the assay of 5-hydroxytryptamine, Br. J. Pharmacol. Chemother., 12: 344–349.PubMedGoogle Scholar
  68. Vizi, V.A., and Vizi, E.S., 1978, Direct evidence for acetylcholine releasing effect of serotonin in the Auerbach’s plexus, J. Neural Transm., 42: 127–138.PubMedCrossRefGoogle Scholar
  69. Wade, P.R., Branchek, T.A., Mawe, G.M., and Gershon, M.D., 1990, Use of stereoisomers of Zacopride to distinguish between 5-HT receptor subtypes: an intracellular study of myenteric neurons and gastric emptying, Proc. N.Y. Acad. Sci., in press.Google Scholar
  70. Wallis, D.I., Stansfeld, C.E., and Nash, N.L., 1982, Depolarizing responses recorded from nodose ganglion cells in the rabbit evoked by 5-hydroxytryptamine and other substances, Neuropharmacology, 21: 31–40.PubMedCrossRefGoogle Scholar
  71. Wood, J.D., 1987, Physiology of enteric neurons, in: “Physiology of the Gastrointestinal Tract”, Johnson, L.R., ed., Vol. 1, 2nd Edition, Raven Press, New York, pp. 1–41.Google Scholar
  72. Wood, J.D., and Mayer, C.J., 1979, Serotonergic activation of tonic-type enteric neurons in guinea pig small bowel, J. Neurophysiol., 422: 582–593.Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • M. D. Gershon
    • 1
  1. 1.Department of Anatomy and Cell BiologyColumbia University, College of Physicians and SurgeonsNew YorkUSA

Personalised recommendations