Agonist-induced down-regulation of human 5-HT1A and 5-HT2 receptors in Swiss 3T3 cells

Neuroreport. 1993 Sep 30;4(12):1327-30. doi: 10.1097/00001756-199309150-00010.


We have used single cell clones of Swiss 3T3 cells transfected with genes for the human 5-HT1A or 5-HT2 receptor to study down-regulation and desensitization. After pre-incubation of the cells with serotonin agonists, a time-dependent decrease in [3H]8-hydroxy-2-(di-n-propylamino) tetralin or [3H]ketanserin binding was observed. The pertussis toxin sensitive, 5-HT mediated inhibition of forskolin-stimulated cAMP accumulation in 5-HT1A receptor transfected cells was diminished by 68% after a 2 h pre-incubation of the cells with 10 microM 5-HT. The pertussis toxin insensitive, 5-HT mediated PI turnover in 5-HT2 receptor transfected cells was decreased by 65% after pre-treatment. While this decrease was paralleled by a decreased potency of 5-HT to stimulate PI turnover, in 5-HT1A cells the potency of 5-HT to inhibit cAMP formation was comparable to control values. The down-regulation and desensitization of the 5-HT2 receptor can be explained by phosphorylation via activated PKC. In contrast, the attenuation of the 5-HT1A receptor-coupled inhibition of cAMP accumulation has to occur by an alternative, as yet unknown, molecular mechanism.

MeSH terms

  • 3T3 Cells
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Down-Regulation / drug effects*
  • Humans
  • Hydrolysis
  • Ketanserin / metabolism
  • Kinetics
  • Mice
  • Mice, Inbred Strains
  • Pertussis Toxin
  • Phosphatidylinositols / metabolism
  • Receptors, Serotonin / drug effects*
  • Serotonin / pharmacology
  • Serotonin Antagonists
  • Virulence Factors, Bordetella / pharmacology


  • Phosphatidylinositols
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Virulence Factors, Bordetella
  • Colforsin
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Ketanserin
  • Cyclic AMP
  • Pertussis Toxin