Development of a radioligand binding assay for 5-HT4 receptors in guinea-pig and rat brain

Br J Pharmacol. 1993 Jul;109(3):618-24. doi: 10.1111/j.1476-5381.1993.tb13617.x.


1. The 5-HT4 receptor antagonist, GR113808, has been radiolabelled to a high specific activity with tritium. 2. Characterization of specific [3H]-GR113808 binding in homogenates of guinea-pig striatum and hippocampus revealed a single site of high affinity (Kd values 0.20 and 0.13 nM respectively). 3. [3H]-GR113808 binding was reversible and displayed rapid kinetics such that association and dissociation were complete within 3 min. 4. Specific [3H]-GR113808 binding was potently and stereoselectively inhibited by agonists and antagonists acting at the 5-HT4 receptor but not by compounds selective for other 5-HT receptors or other neurotransmitter receptors. 5. Autoradiographic analysis revealed a discrete localization in both guinea-pig and rat brain with high concentrations of binding in brain areas such as the striatum, substantia nigra and olfactory tubercle. 6. [3H]-GR113808 binding to homogenates of guinea-pig striatum meets the criteria for labelling of the 5-HT4 receptor and, as such, represents the first characterization of this receptor in a radioligand binding assay.

MeSH terms

  • Animals
  • Autoradiography
  • Binding, Competitive / drug effects
  • Brain Chemistry / drug effects*
  • Corpus Striatum / metabolism
  • Guinea Pigs
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Indoles / pharmacokinetics*
  • Nerve Tissue Proteins / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Serotonin / drug effects*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Stereoisomerism
  • Sulfonamides / pharmacokinetics*


  • Indoles
  • Nerve Tissue Proteins
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Sulfonamides
  • GR 113808