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Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal. fmartel@med.up.pt
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.
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