The effect of high glucose on SERT, the human plasmalemmal serotonin transporter.
The aim of this work was to investigate the effect of short- and long-term high-glucose exposure on the plasmalemmal serotonin transporter (SERT)-mediated uptake of [(3)H]-serotonin (5-HT) by Caco-2 cells. Short-term exposure of Caco-2 cells to high apical glucose levels (30 mM for 2 h or 40 mM for 1 h) decreased the uptake of [(3)H]-5-HT by 20-30%. On the other hand, long-term (21-24 weeks) exposure of the cells to high (25 mM) glucose caused a 30% increase in the uptake of [(3)H]5-HT. Under these conditions, the affinity of the transporter for 5-HT and noradrenaline was not significantly changed, and the inhibitory potencies of fluoxetine and desipramine were also unchanged. In conclusion, high-glucose levels modulate SERT activity. A short-term exposure of the cells to a high concentration of glucose decreases the activity of the transporter, whereas a longer exposure of the cells to a high concentration of glucose increases the activity of SERT, without interfering with its affinity.
Gonçalves
Pedro
P
Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal. fmartel@med.up.pt
Araújo
João R
JR
Martel
Fátima
F
D018938:Caco-2 Cells; D005937:Glucaric Acid / Q000008:administration & dosage*; D006801:Humans; D007700:Kinetics; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors; D014316:Tritium
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014316:Tritium; D012701:Serotonin; D005937:Glucaric Acid; D009638:Norepinephrine