Serotonin (5-hydroxytryptamine [5-HT]) is an important neurotransmitter that regulates multiple events in the central nervous system (CNS). We have recently demonstrated that 5-HT4 receptor couples to G13 protein to induce RhoA-dependent gene transcription, neurite retraction, and neuronal cell rounding (Ponimaskin et al, 2002). Although multiple studies were focused on the function of the 5-HT4 receptor in the CNS, none of the studies showed its expression and function in the endothelial cells. In the present study, we provide evidence for the first time that 5-HT4 receptor is expressed in the human umbilical vein endothelial cells (HUVECs). We demonstrate the transcription of 5-HT4 mRNA in the HUVECs using reverse transcription polimerase chain reaction. Additionally, we show 5-HT4 receptor expression in HUVECs by immunoblotting and immunofluorescent analysis with 5-HT4 specific antibody. Importantly, we determine that overexpression of 5-HT4 receptor leads to a pronounced cell rounding and intercellular gap formation in HUVECs. We are currently investigating the mechanism underlying 5-HT4 receptor-induced actin cytoskeleton changes in the endothelial cells. These data suggest that by activating 5-HT4 receptor, serotonin could be involved in regulation of actin cytoskeleton dynamics in the endothelial cells that may affect the endothelial barrier integrity.
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