Discriminating between 5-HT₃A and 5-HT₃AB receptors

Br J Pharmacol. 2013 Jun;169(4):736-47. doi: 10.1111/bph.12166.

Abstract

The 5-HT3B subunit was first cloned in 1999, and co-expression with the 5-HT3A subunit results in heteromeric 5-HT₃AB receptors that are functionally distinct from homomeric 5-HT₃A receptors. The affinities of competitive ligands at the two receptor subtypes are usually similar, but those of non-competitive antagonists that bind in the pore often differ. A competitive ligand and allosteric modulator that distinguishes 5-HT₃A from 5-HT₃AB receptors has recently been described, and the number of non-competitive antagonists identified with this ability has increased in recent years. In this review, we discuss the differences between 5-HT₃A and 5-HT₃AB receptors and describe the possible sites of action of compounds that can distinguish between them.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation / drug effects
  • Animals
  • Antiemetics / chemistry
  • Antiemetics / metabolism
  • Antiemetics / pharmacology
  • Antiemetics / therapeutic use
  • Binding Sites / drug effects
  • Binding, Competitive / drug effects
  • Drug Partial Agonism
  • Humans
  • Ligands
  • Models, Molecular*
  • Molecular Conformation
  • Protein Multimerization
  • Protein Subunits / antagonists & inhibitors
  • Protein Subunits / chemistry
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Receptors, Serotonin, 5-HT3 / chemistry
  • Receptors, Serotonin, 5-HT3 / genetics
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Serotonin 5-HT3 Receptor Agonists / chemistry
  • Serotonin 5-HT3 Receptor Agonists / metabolism
  • Serotonin 5-HT3 Receptor Agonists / pharmacology
  • Serotonin 5-HT3 Receptor Agonists / therapeutic use
  • Serotonin 5-HT3 Receptor Antagonists / chemistry
  • Serotonin 5-HT3 Receptor Antagonists / metabolism
  • Serotonin 5-HT3 Receptor Antagonists / pharmacology
  • Serotonin 5-HT3 Receptor Antagonists / therapeutic use

Substances

  • Antiemetics
  • HTR3A protein, human
  • HTR3B protein, human
  • Ligands
  • Protein Subunits
  • Receptors, Serotonin, 5-HT3
  • Recombinant Proteins
  • Serotonin 5-HT3 Receptor Agonists
  • Serotonin 5-HT3 Receptor Antagonists