Serotonin 5-HT2C receptor RNA editing alters receptor basal activity: implications for serotonergic signal transduction

J Neurochem. 1999 Oct;73(4):1711-7. doi: 10.1046/j.1471-4159.1999.731711.x.


Rat and human serotonin 5-HT2C receptor isoforms were evaluated for agonist-independent activation of inositol phosphate production in COS-7 cells. The nonedited isoform (5-HT(2C-INI)) displayed the greatest basal activity, stimulating inositol phosphate production fourfold over the fully edited isoform (5-HT(2C--VGV)). All of the other isoforms tested displayed intermediate levels of basal activity. Decreasing receptor expression levels by 50% produced a parallel decrease in basal activity. 5-HT stimulated inositol phosphate production twofold over basal levels through the 5-HT(2C-INI) receptor and eightfold over basal levels through the 5-HT(2C-VGV) receptor but produced similar maximal levels of inositol phosphate. 5-HT competition for [3H]mesulergine binding to 5-HT(2C-INI) best fit a two-site analysis with K(H) = 7.6 nM and K(L) = 160 nM, whereas 5-HT(2C-VGV) best fit a one-site model with Ki = 163 nM. [3H]5-HT labeled 36% of the total population of 5-HT(2C-INI) receptors labeled by [3H]mesulergine but only 12% of 5-HT(2C-VGV) receptors. [H]5-HT K(D) values increased from 5.1 nM for 5-HT(2C-INI) to 20 nM for 5-HT(2C-VGV). [3H]Mesulergine K(D) values were the same for both isoforms. 5-HT EC50 values for inositol phosphate production increased from 6.1 nM for 5-HT(2C-INI) to 30 nM for 5-HT(2C-VGV). These results demonstrate that RNA editing decreases 5-HT2C receptor basal activity, agonist affinity, and potency, indicating that RNA editing may play a role in regulating serotonergic signal transduction and response to drug therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • COS Cells
  • Ergolines / pharmacokinetics
  • Humans
  • Inositol Phosphates / metabolism
  • Kinetics
  • Mianserin / pharmacology
  • Mutagenesis, Site-Directed
  • Pargyline / pharmacology
  • RNA Editing*
  • Rats
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / genetics*
  • Receptors, Serotonin / physiology*
  • Recombinant Proteins / metabolism
  • Serotonin / metabolism*
  • Serotonin Antagonists / pharmacokinetics
  • Signal Transduction*
  • Transfection


  • Ergolines
  • Inositol Phosphates
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Recombinant Proteins
  • Serotonin Antagonists
  • Mianserin
  • Serotonin
  • Pargyline
  • mesulergine