Characterization of a putative intrarenal serotonergic system.

Xu J, Yao B, Fan X, Langworthy MM, Zhang MZ, Harris RC
Am J Physiol Renal Physiol. 2007 293 (5): F1468-75

PMID: 17715266 · DOI:10.1152/ajprenal.00246.2007

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.

MeSH Terms (26)

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

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