5-HT activates ERK MAP kinase in cultured-human peripheral blood mononuclear cells via 5-HT sub(1A) receptors

In the present work, we tested the hypothesis that serotonin (5- hydroxytryptamine = 5-HT) might activate the extracellular signal-regulated kinase (ERK) pathway in human peripheral blood mononuclear cells (PBMC). PBMC were maintained in culture for 72 hrs at 37C prior to the addition of 5-HT. Our results showed an increase in ERK activation by 5-HT with a peak effect at 30 min and maximal stimulation with 5-HT at 1 mu M. This activation of ERK did not occur in adherent monocytes suggesting that the effect was on lymphocytes. In addition, p38 MAP kinase was not activated under these conditions. The effect of 5-HT on ERK activation appeared to be mediated through the activation of 5- HT sub(1A) receptors since similar results were obtained with R-(+)-8-hydroxy- DPAT, a selective 5-HT sub(1A) receptor agonist and WAY100635, a selective 5- HT sub(1A) receptor antagonist, reversed the 5-HT and the R-(+)-8-hydroxy-DPAT effects. Results from Western blot analysis confirmed the presence of 5-HT sub(1A) receptors on the PBMC. A 5-HT sub(2A) antagonist, ketanserin, and a 5-HT transport inhibitor, fluoxetine, both failed to block the activation of ERK by 5-HT. Our results indicate that 5-HT activates ERK, but not p38, MAP kinase of human PBMC via a 5-HT sub(1A) receptor.