D-glucose releases 5-hydroxytryptamine from human BON cells as a model of enterochromaffin cells.
OBJECTIVE
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.
Kim
M
M
Department of Pharmacology, The Ohio State University, 333 West 10th Avenue, Columbus, OH 43210, USA.
Cooke
H J
HJ
Javed
N H
NH
Carey
H V
HV
Christofi
F
F
Raybould
H E
HE
D020126:Brefeldin A / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000378:metabolism*; D005632:Fructose / Q000494:pharmacology; D005690:Galactose / Q000494:pharmacology; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D008353:Mannitol / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008757:Methylglucosides / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D010695:Phlorhizin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1
D008562:Membrane Glycoproteins; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D051269:Sodium-Glucose Transporter 1; D005576:Colforsin; D020126:Brefeldin A; D005632:Fructose; D012701:Serotonin; D008353:Mannitol; C027020:methylglucoside; D010695:Phlorhizin; D005947:Glucose; D005690:Galactose