Identification and characterisation of 5-hydroxytryptamine 3 recognition sites in human brain tissue

J Neurochem. 1989 Dec;53(6):1787-93. doi: 10.1111/j.1471-4159.1989.tb09244.x.


[3H]Zacopride displayed regional saturable specific binding to homogenates of human brain tissues, as defined by the inclusion of BRL43694 [endo-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1-methylindazole-3- carboxamide] in the incubation media. Scatchard analysis of the saturation data obtained from amygdaloid and hippocampal tissues identified the binding as being of high affinity and to a homogeneous population of binding sites (KD = 2.64 +/- 0.75 and 2.93 +/- 0.41 nmol/L and Bmax = 55 +/- 7 and 44 +/- 9 fmol/mg of protein in the amygdala and hippocampus, respectively). 5-Hydroxytryptamine 3 (5-HT3) receptor agonists and antagonists competed for the [3H]zacopride binding site, competing with up to 40% of total binding with a similar rank order of affinity in both tissues; agents acting on various other neurotransmitter receptors failed to inhibit binding. Kinetic data revealed a fast association that was fully reversible (k+1 = 6.61 X 10(5) and 7.65 X 10(5)/mol/L/s and k-1 = 3.68 X 10(-3) and 3.45 X 10(-3)/s in the amygdala and hippocampus, respectively). It is concluded that [3H]zacopride selectively labels with high affinity 5-HT3 recognition sites in human amygdala and hippocampus and, if these binding domains represent 5-HT3 receptors, may provide the opportunity for 5-HT3 receptor antagonists to modify 5-HT function in the human brain.

MeSH terms

  • Adult
  • Aged
  • Amygdala / metabolism
  • Benzamides / metabolism
  • Binding, Competitive
  • Brain / metabolism*
  • Bridged Bicyclo Compounds / metabolism
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Hippocampus / metabolism
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Receptors, Serotonin / metabolism*
  • Serotonin Antagonists / metabolism
  • Tritium


  • Benzamides
  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Tritium
  • zacopride