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

Peter Brust, Anne Friedrich, I. Krizbai, Ralf Bergmann, Françoise Roux, Vadivel Ganapathy, Bernd Johannsen

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

There is evidence from recent studies that the brain endothelium (of capillaries and/or larger vessels) may serve as a specific target for serotonin [5-hydroxytryptamine (5-HT)]. This neurotransmitter is expected to be involved in the regulation of the blood-brain barrier (BBB) permeability and/or of the cerebral blood flow via receptor-mediated mechanisms. Effective control 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-PCR that 5-HT transporter mRNA is present in the brain endothelium and that a saturable transport system for 5-HT is functionally expressed in immortalized rat brain endothelial cells (RBE4 cells). These cells take up [3H]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 depends on Na+, as indicated by the replacement of NaCl by LiCl. The 5-HT uptake was sensitive to specific 5-HT transport inhibitors such as paroxetine, clomipramine, fluoxetine, and citalopram but not to inhibitors of the vesicular amine transporter such as reserpine or tetrabenazine. Our results demonstrate that cerebral endothelial cells are able to participate actively in the removal and metabolism of the released 5-HT, which supports the concept of direct serotoninergic regulation of the BBB function.

Original languageEnglish
Pages (from-to)1241-1248
Number of pages8
JournalJournal of Neurochemistry
Volume74
Issue number3
Publication statusPublished - 2000

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Endothelial cells
Microvessels
Rats
Brain
Serotonin
Endothelial Cells
Blood-Brain Barrier
Vesicular Biogenic Amine Transport Proteins
Metabolism
Cerebrovascular Circulation
Tetrabenazine
Clomipramine
Paroxetine
Citalopram
Fluoxetine
Reserpine
Vascular Endothelium
Endothelium
Neurotransmitter Agents

Keywords

  • Blood-brain barrier
  • Citalopram
  • Clomipramine
  • Fluoxetine
  • Gene expression
  • Paroxetin e
  • Serotonin
  • Transporter

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Brust, P., Friedrich, A., Krizbai, I., Bergmann, R., Roux, F., Ganapathy, V., & Johannsen, B. (2000). Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells. Journal of Neurochemistry, 74(3), 1241-1248.

Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells. / Brust, Peter; Friedrich, Anne; Krizbai, I.; Bergmann, Ralf; Roux, Françoise; Ganapathy, Vadivel; Johannsen, Bernd.

In: Journal of Neurochemistry, Vol. 74, No. 3, 2000, p. 1241-1248.

Research output: Contribution to journalArticle

Brust, P, Friedrich, A, Krizbai, I, Bergmann, R, Roux, F, Ganapathy, V & Johannsen, B 2000, 'Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells', Journal of Neurochemistry, vol. 74, no. 3, pp. 1241-1248.
Brust, Peter ; Friedrich, Anne ; Krizbai, I. ; Bergmann, Ralf ; Roux, Françoise ; Ganapathy, Vadivel ; Johannsen, Bernd. / Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells. In: Journal of Neurochemistry. 2000 ; Vol. 74, No. 3. pp. 1241-1248.
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