Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

The 5-HT3 Receptor

  • Sarah C. R. Lummis
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_647

Synonyms

Historical Background

5-Hydroxytryptamine (5-HT), also known as serotonin, was initially identified as a potent vasoconstrictor present in blood serum (Rapport et al. 1947), but it has become obvious over the years that 5-HT has a multitude of functions, including activation or inhibition of muscle, exocrine and endocrine glands, central and peripheral neurons, and cells of the hematopoietic and immune systems. 5-HT initiates its actions by binding to specific receptor proteins in the cell membrane. These 5-HT receptors were initially subdivided into D and M subtypes, based on their sensitivity to dibenyline or morphine (Gaddum and Picarelli 1957). This was an oversimplification, and currently 5-HT receptors are divided into seven major families (5-HT1–7) based on transduction and structural characteristics. All of these receptors exert their effects via G proteins, except for the 5-HT3receptor which is a ligand-gated ion channel...

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

References

  1. Barnes NM, Hales TG, Lummis SC, Peters JA. The 5-HT3 receptor--the relationship between structure and function. Neuropharmacology. 2009;56:273–84.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Davies PA. Allosteric modulation of the 5-HT3 receptor. Curr Opin Pharmacol. 2011;11:75–80.Google Scholar
  3. Davies PA, Pistis M, Hanna MC, Peters JA, Lambert JJ, Hales TG, Kirkness EF. The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature. 1999;397:359–63.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Gaddum JH, Picarelli ZP. Two kinds of tryptamine receptor. Br J Pharmacol Chemother. 1957;12:323–8.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Goyal R, Salahudeen AA, Jansen M. Engineering a prokaryotic Cys-loop receptor with a third functional domain. J Biol Chem. 2011;286:34635–42.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Hassaine G, Deluz C, Grasso L, Wyss R, Tol MB, Hovius R, Graff A, Stahlberg H, Tomizaki T, Desmyter A, Moreau C, Li XD, Poitevin F, Vogel H, Nury H. X-ray structure of the mouse serotonin 5-HT3 receptor. Nature. 2014;512:276–81.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Holbrook JD, Gill CH, Zebda N, et al. Characterisation of 5-HT3C, 5-HT3D and 5-HT3E receptor subunits: evolution, distribution and function. J Neurochem. 2009;108:384–96.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Kelley SP, Dunlop JI, Kirkness EF, Lambert JJ, Peters JA. A cytoplasmic region determines single-channel conductance in 5-HT 3 receptors. Nature. 2003;424:321–4.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Lummis SCR. 5-HT3 receptors. J. Biol. Chem. 2012;287:40239–45.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Machu TK. Therapeutics of 5-HT3 receptor antagonists: current uses and future directions. Pharmacol Ther. 2011;130:338–47.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Mawe GM, Hoffman JM. Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol. 2013;10:473–86.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Niesler B. 5-HT3 receptors: potential of individual isoforms for personalised therapy. Curr Opin Pharmacol. 2011;11:81–6.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Niesler B, Frank B, Kapeller J, Rappold GA. Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E. Gene. 2003;310:101–11.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Niesler B, Walstab J, Combrink S, Moller D, Kapeller J, Rietdorf J. Characterization of the novel human serotonin receptor subunits 5-HT3C,5-HT3D, and 5-HT3E. Mol Pharmacol. 2007;72:8–17.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Nys M, Kesters D, Ulens C. Structural insights into Cys-loop receptor function and ligand recognition. Biochem Pharmacol. 2013;86:1042–53.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Peters JA, Cooper MA, Carland JE, Livesey MR, Hales TG, Lambert JJ. Novel structural determinants of single channel conductance and ion selectivity in 5-hydroxytryptamine type 3 and nicotinic acetylcholine receptors. J Physiol. 2010;588:587–96.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Rapport MM, Green A, Page IH. Purification of the substance which is responsible for the vasoconstrictor activity of serum. Fed Proc. 1947;6:184.PubMedPubMedCentralGoogle Scholar
  18. Thompson AJ, Lummis SCR. 5-HT3 receptors. Curr Pharm Des. 2006;12:3615–30.Google Scholar
  19. Thompson AJ, Lummis SCR. The 5-HT3 receptor as a therapeutic target. Expert Opin Ther Targets. 2007;11:527–40.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Thompson AJ, Lester HA, Lummis SCR. The structural basis of function in Cys-loop receptors. Q Rev Biophys. 2010;43:449–99.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Thompson AJ, Lummis SCR. Discriminating between 5-HT3A and 5-HT3AB receptors. Br J Pharmacol. 2013;169:736–747.Google Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of CambridgeCambridgeUK