Characterization of a putative intrarenal serotonergic system

Am J Physiol Renal Physiol. 2007 Nov;293(5):F1468-75. doi: 10.1152/ajprenal.00246.2007. Epub 2007 Aug 22.


Serotonin [5-hydroxytryptamine (5HT)] acts through multiple G protein-coupled 5-HT receptors, and its activity is also regulated by the 5-HT transporter. The current studies report the expression and localization of the 5-HT receptors and transporter in the kidney. In addition, the enzymatic pathway mediating 5-HT synthesis is present in renal cortex, especially in the proximal tubules and glomerular epithelial cells and mesangial cells. Expression of the 5-HT receptors and 5-HT transporter was detected by RT-PCR in cell lines of these cell types. In cultured proximal tubule cells and podocytes, 5-HT activated ERK1/2 and increased the expression of connective tissue growth factor and transforming growth factor-beta, two key mediators of extracellular matrix accumulation. Immunohistochemistry and real-time RT-PCR studies also indicated that 5-HT stimulated expression of vascular endothelial growth factor in podocytes in vitro and in vivo. Therefore, these results indicate the presence of an integrated intrarenal serotonergic system and suggest a possible role for 5-HT as a mediator of renal fibrosis in the kidney.

Publication types

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

MeSH terms

  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism*
  • Cell Line
  • Connective Tissue Growth Factor
  • Immediate-Early Proteins / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Kidney Cortex / metabolism*
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / metabolism
  • Male
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Phosphorylation / drug effects
  • Podocytes / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Receptors, Serotonin / metabolism*
  • Serotonin / metabolism
  • Serotonin / pharmacology
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Signal Transduction / physiology
  • Tissue Distribution
  • Transforming Growth Factor beta / metabolism
  • Tryptophan Hydroxylase / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism


  • CCN2 protein, mouse
  • CCN2 protein, rat
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • Serotonin Plasma Membrane Transport Proteins
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Connective Tissue Growth Factor
  • Serotonin
  • Tryptophan Hydroxylase
  • Mitogen-Activated Protein Kinase Kinases
  • Aromatic-L-Amino-Acid Decarboxylases