Serotonin and its transporter on proliferation of fetal heart cells

Int J Dev Neurosci. 2003 Dec;21(8):417-24. doi: 10.1016/j.ijdevneu.2003.10.002.


Besides neuronal transmission, serotonin (5-HT) also acts as a trophic signal during the development of the central nervous and neural crest systems. In this study, we report that in addition to trophic effect, 5-HT increases the proliferation of fetal heart cells. We showed for the first time that the cultured heart cells, express serotonin transporter (5-HTT), which confirmed the previously observed accumulation of 5-HT in developing heart. The influence of 5-HT on developing heart cells is studied throughout the dosage. We found that 5-HT concentration at physiological level, 4 microM, permits an optimal proliferation of heart cells as indicated by the number of 5-bromo-deoxyuridine immunoreactive (BrdU-im) cells and myosin heavy chain immunoreactive cells (MF20-im); fluctuation towards either concentrations reduce the proliferation. We hypothesized that 5-HTT plays a role in the heart development. Our study indicated that the blockade of 5-HT uptake by paroxetine decreased the number of BrdU-im cells and MF20-im cells. These data indicate a role of 5-HT and 5-HTT on heart development. Abnormal 5-HT level or misuse of 5-HT uptake blocker may alter the heart development.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Bromodeoxyuridine / metabolism
  • Carrier Proteins / metabolism*
  • Cell Count
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Embryo, Mammalian
  • Female
  • Fetal Heart / cytology*
  • Fetal Heart / metabolism
  • Immunohistochemistry
  • Male
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myosin Heavy Chains / metabolism
  • Nerve Tissue Proteins*
  • Paroxetine / pharmacology
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors / pharmacology


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Slc6a4 protein, rat
  • Serotonin
  • Paroxetine
  • Myosin Heavy Chains
  • Bromodeoxyuridine