Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells

There is evidence from recent studies that the brain endothelium (of capill aries and/or larger vessels) may serve as a specific target for serotonin [ 5-hydroxytryptamine (5-HT)]. This neurotransmitter is expected to be involv ed in the regulation of the blood-brain barrier (BBB) permeability and/or o f the cerebral blood flow via receptor-mediated mechanisms. Effective contr ol of these processes depends on a speedy uptake and metabolism of released 5-HT molecules. To realize this, a similar mechanism of 5-HT uptake as in brain may exist at the BBB, In this study, we have demonstrated using RT-PC R that 5-HT transporter mRNA is present in the brain endothelium and that a saturable transport system for 5-HT is functionally expressed in immortali zed rat brain endothelial cells (RBE4 cells). These cells take up [H-3]5-HT by an active saturable process with a K-m value of 397 +/- 64 nmol/L and a transport capacity of 51.7 +/- 3.5 pmol.g(-1).min(-1). The 5-HT uptake dep ends on Na+, as indicated by the replacement of NaCl by LiCl. The 5-HT upta ke was sensitive to specific 5-HT transport inhibitors such as paroxetine, clomipramine, fluoxetine, and citalopram but not to inhibitors of the vesic ular amine transporter such as reserpine or tetrabenazine. Our results demo nstrate that cerebral endothelial cells are able to participate actively in the removal and metabolism of the released 5-HT, which supports the concep t of direct serotoninergic regulation of the BBB function.