• DOI:10.1152/ajplung.1999.277.2.L282
• Corpus ID: 25040770

Serotonin stimulates mitogen-activated protein kinase activity through the formation of superoxide anion.

@article{Lee1999SerotoninSM,
  title={Serotonin stimulates mitogen-activated protein kinase activity through the formation of superoxide anion.},
  author={S. L. Lee and W W Wang and Geraldine A. Finlay and Barry L Fanburg},
  journal={The American journal of physiology},
  year={1999},
  volume={277 2},
  pages={
          L282-91
        }
}

• S. L. Lee, W. -. Wang, +1 author B. Fanburg
• Published 1 August 1999
• Biology
• The American journal of physiology

Our previous studies have shown that, through an active transport process, serotonin (5-HT) rapidly elevates O(-)(2). formation, stimulates protein phosphorylation, and enhances proliferation of bovine pulmonary artery smooth muscle cells (SMCs). We presently show that 1 microM 5-HT also rapidly elevates phosphorylation and activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) 1 and ERK2 of SMCs, and the enhanced phosphorylation is blocked by the antioxidants Tiron, N-acetyl-L-cysteine (NAC), and Ginkgo biloba extract. Inhibition of MAP kinase with PD-98059 failed to block enhanced O(-)(2). formation by 5-HT. Chinese hamster lung fibroblasts (CCL-39 cells), which demonstrate both 5-HT transporter and receptor activity, showed a similar response to 5-HT (i.e., enhanced mitogenesis, O(-)(2). formation, and ERK1 and ERK2 phosphorylation and activation). Unlike SMCs, they also responded to 5-HT receptor agonists. We conclude that downstream signaling of MAP kinase is a generalized cellular response to 5-HT that occurs secondary to O(-)(2). formation and may be initiated by either the 5-HT transporter or receptor depending on the cell type.