Effects of Antidepressants on Intracellular Ca2+ Mobilization in CHO Cells Transfected With the Human 5-HT2C Receptors

Biol Psychiatry. 1996 Jun 15;39(12):1000-8. doi: 10.1016/0006-3223(95)00309-6.


Serotonin 5-HT2C receptor-mediated intracellular Ca2+ mobilization was investigated in 5-HT2C receptors expressed in Chinese hamster ovary (CHO) cells; and fura-2/AM was used to investigate the regulation of 5-HT2C receptor function. CHO cells, transfected with a cDNA clone for the 5-HT2C receptor, expressed 287 fmol/mg of the receptor protein as determined by mianserin-sensitive [3H]-mesulergine binding (kd = 0.49 nM). The addition of 5-HT mobilized intracellular Ca2+ in a dose-dependent fashion, ranging from basal level of 99 +/- 1.8 nM up to 246 +/- 21.2 nM, with an EC50 value for 5-HT of .015 microM. Exposure to 5-HT, a 5-HT receptor agonist, mCPP [1-(3-chlorophenyl)piperazine dihydrochloride], a 5-HT2C agonist, and DOI [1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane], a 5-HT2C and 5-HT2 agonist, resulted in increased intracellular Ca2+ levels. Mianserin, mesulergine, ritanserin, and ketanserin each blocked 5-HT-mediated intracellular Ca2+ mobilization more effectively than spiperone. Mianserin and amoxapine inhibited 5-HT-mediated intracellular Ca2+ mobilization completely; amitriptyline, nortriptyline, and imipramine reduced it about 50%. These results suggest that antagonism in CHO cells transfected with human 5-HT2C receptors is a component of the serotonergic properties of a number of established antidepressants.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents, Second-Generation / pharmacology
  • CHO Cells
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / genetics*
  • Cricetinae
  • Ergolines / pharmacokinetics
  • Humans
  • Intracellular Fluid / drug effects*
  • Mianserin / pharmacology
  • Radioligand Assay
  • Receptors, Serotonin / classification
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / genetics*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Transfection / genetics*


  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Calcium Channels
  • Ergolines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Mianserin
  • mesulergine
  • Calcium