D-glucose releases 5-hydroxytryptamine from human BON cells as a model of enterochromaffin cells

Background & Aims: 5-Hydroxytryptamine (5-HT) is released from enterochromaffin cells and activates neural reflex programs regulating motility and secretion. Although sugars are reported to release 5-HT in vivo, it is unclear whether they act directly on enterochromaffin cells or indirectly through an intermediary messenger. The aim was to determine if D-glucose is a stimulus for 5-HT release. Methods: Human BON cells, derived from enterochromaffin cells, were treated with D-glucose, galactose, and the nonmetabolizable methyl alpha -D-glucopyranoside, or with fructose. Results: Reverse-transcription polymerase chain reaction together with Western blot analysis revealed an SGLT-like protein. D-Glucose caused a concentration-dependent increase in 5-HT release, which was mimicked by methyl alpha -D-glucopyranoside and galactose but not fructose. D-Glucose-stimulated 5-HT release was significantly reduced by phloridzin. Concentrations of mannitol below 75 mmol/L were ineffective in releasing 5-HT. Brefeldin A abolished forskolin-stimulated 5-HT release without affecting basal or constitutive release. Conclusions: The results show that high concentrations of metabolizable and nonmetabolizable hexoses activate signal transduction pathways, leading to release of 5-HT. These findings imply a role for enterochromaffin cells as "glucose sensors" during ingestion of a meal.