5-Hydroxyindole potentiates human alpha 7 nicotinic receptor-mediated responses and enhances acetylcholine-induced glutamate release in cerebellar slices

Neuropharmacology. 2002 Sep;43(3):374-84. doi: 10.1016/s0028-3908(02)00094-1.


The effects of 5-hydroxyindole (5-HI) have been investigated on human alpha 7 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes and GH4 cells, on native alpha 7 nAChRs expressed by IMR-32 cells and on alpha 7 nAChR-mediated events in mossy fibre-granule cell synapses in rat cerebellar slices. In oocytes expressing alpha 7 nAChRs, 5-HI potentiated sub-maximal, 60 micro M ACh-induced ion currents in a concentration-dependent manner, the threshold effective concentration being 30 micro M. 5-HI itself did not act as an agonist on alpha 7 nAChRs. A maximum potentiation of 12 times the control was observed at 20 mM 5-HI. The effect of 1 mM 5-HI on the concentration-response curve for ACh revealed that 5-HI increased the potency as well as the efficacy of ACh on alpha 7 nAChRs. 5-HI also potentiated alpha 7-mediated increases in intracellular free calcium levels in both mammalian cells heterologously expressing human alpha 7 nAChRs and in human IMR-32 neuroblastoma cells expressing native alpha 7 nAChRs. At mossy fibre-granule cell synapses, application of 1 mM ACh induced glutamate-evoked excitatory post-synaptic currents (EPSCs). Co-application of 1 mM 5-HI with 1 mM ACh further increased the frequency of the EPSCs. The ACh-induced release, as well as the 5-HI-induced enhancement of release, were blocked by 1-10 nM methyllycaconitine or 200 nM alpha-bungarotoxin, demonstrating that both effects were mediated by presynaptic alpha 7 nAChRs. The results demonstrate that responses mediated by alpha 7 nAChRs are strongly potentiated by 5-HI.

MeSH terms

  • Acetylcholine / pharmacology*
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Cerebellum / drug effects
  • Cerebellum / metabolism*
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Female
  • Glutamic Acid / metabolism*
  • Image Processing, Computer-Assisted
  • In Vitro Techniques
  • Indoles / pharmacology*
  • Membrane Potentials / physiology
  • Microelectrodes
  • Oocytes / drug effects
  • Patch-Clamp Techniques
  • Rats
  • Receptors, Nicotinic / drug effects*
  • Synaptic Transmission / drug effects
  • Xenopus laevis
  • alpha7 Nicotinic Acetylcholine Receptor


  • Chrna7 protein, human
  • Chrna7 protein, rat
  • Indoles
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • 5-hydroxyindole
  • Glutamic Acid
  • Acetylcholine
  • Calcium