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Serotonin: Its Role and Receptors in Enteric Neurotransmission

  • Chapter
Kynurenine and Serotonin Pathways

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 294))

Abstract

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.

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References

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Branchek, T.A., and Gershon, M.D., 1987, Development of neural receptors for serotonin in the murine bowel, J. Comp. Neurol., 258: 597–610.

    Article  PubMed  CAS  Google Scholar 

  • Branchek, T.A., Kates, M., and Gershon, M.D., 1984b, Enteric receptors for 5-hydroxytryptamine, Brain Res., 324: 107–118.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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 

  • 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 

  • Brownlee, G., and Johnson, E.S., 1963, The site of the 5-hydroxytryptamine receptor on the peristaltic reflex, Br. J. Pharmacol., 21: 306–322.

    CAS  Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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 

  • Cassuto, J., Jodal, M., Tuttle, R., and Lundgren, O., 1982, 5-Hydroxytryptamine and cholera secretion, Scand. J. Gastroenterol., 17: 695–703.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Davidson, H.I., and Pilot, M.A., 1986, Does endogenous neuronal 5-hydroxytryptamine influence canine intestinal motility, J. Physiol. (London), 376:49P.

    Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    PubMed  CAS  Google Scholar 

  • Drakontides, A.B., and Gershon, M.D., 1968, 5-HT receptors in the mouse duodenum, Br. J. Pharmacol., 33: 480–492.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Furness, J.B., and Costa, M., 1987, “The Enteric Nervous System”, Churchill, Livingston, New York, pp. 65–69.

    Google Scholar 

  • Gaddum, J.H., and Picarelli, Z.P., 1957, Two kinds of tryptamine receptor, Br. J. Pharmacol. Chemother., 12: 323–328.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Gershon, M.D., 1967, Effects of tetrodotoxin on innervated smooth muscle preparations, Br. J. Pharmacol., 29: 259–279.

    CAS  Google Scholar 

  • Gershon, M.D., 1982, Enteric serotonergic neurons, in: “Biology of Serotonergic Neurotransmission”, Osborne, N., ed., Wiley, New York, pp. 363–399.

    Google Scholar 

  • 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 

  • Gershon, M.D., and Sherman, D.L. 1987, Noradrenergic innervation of serotonergic neurons in the myenteric plexus, J. Comp. Neurol., 259: 193–210.

    Article  PubMed  CAS  Google Scholar 

  • Gershon, M.D., Takaki, M., Tamir, H., and Branchek, T., 1985, The enteric neural receptor for 5-hydroxytryptamine, Experientia, 41: 863–868.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Iversen, L.L., 1963, Uptake of noradrenalin by the isolated perfused rat heart, Br. J. Pharmacol. Chemother., 21: 523–537.

    PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • Julé, Y., 1980, Nerve-mediated descending inhibition in the proximal colon of the rabbit, J. Physiol. (London), 159: 361–368.

    Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Le Douarin, N.M., 1982, “The Neural Crest”, Cambridge, Cambridge University Press.

    Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Nishi, S., and North, R.A., 1973, Intracellular recording from the myenteric plexus of the guinea pig ileum, J. Physiol. (London), 231: 471–491.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Paintal, A.S., 1964, Effects of drugs on vertebrae mechanoreceptors, Pharmacol. Rev., 16: 341–380.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Schaumann, W., 1957, Inhibition by morphine of the release of acetylcholine from the intestine of the guinea pig, Br. J. Pharmacol., 12: 115–118.

    CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Surprenant, A., and Crist, J., 1988, Electrophysiological characterization of functionally distinct 5-HT receptors on guinea-pig submucous plexus, Neuroscience, 24: 283–295.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Vane, J.R., 1957, A sensitive method for the assay of 5-hydroxytryptamine, Br. J. Pharmacol. Chemother., 12: 344–349.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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 

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, New York, 10032, USA

    M. D. Gershon

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  1. M. D. Gershon
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Editors and Affiliations

  1. Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA

    Robert Schwarcz

  2. McGill University, Montreal, Quebec, Canada

    Simon N. Young

  3. University of Wisconsin, Madison, Wisconsin, USA

    Raymond R. Brown

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© 1991 Plenum Press, New York

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Gershon, M.D. (1991). Serotonin: Its Role and Receptors in Enteric Neurotransmission. In: Schwarcz, R., Young, S.N., Brown, R.R. (eds) Kynurenine and Serotonin Pathways. Advances in Experimental Medicine and Biology, vol 294. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5952-4_20

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  • DOI: https://doi.org/10.1007/978-1-4684-5952-4_20

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