Modulation of glucose uptake in glial and neuronal cell lines by selected neurological drugs.

Abstract

Glucose is the main energy source of brain cells. The transport of glucose across the cell membrane is the first step of its utilization. Any modification in glucose uptake capacity may cause deleterious effects on neural cell functions. In the present study, 3-O-methyl-D-glucose (3-OMG) uptake and its modulation by selected neurological drugs (amitriptyline, selegiline, carbamazepine and phenytoin) were studied in differentiated (with retinoic acid and 12-O-tetradecanoyl phorbol 13-acetate) and undifferentiated neuroblastoma SH-SY5Y and astrocytoma U-373 MG cell lines, using tracer methods. The expression of glucose transporters was studied by immunocytochemistry. SH-SY5Y and U-373 MG cells showed differences both in their glucose uptake properties and in the modulation of glucose uptake by the drugs, which might reflect different specialization of neuronal and glial cells in vivo. While selegiline and amitriptyline had a minor and variable effect on 3-OMG uptake in all cell cultures, the anticonvulsants carbamazepine and phenytoin increased 3-OMG uptake in U-373 MG cells, but decreased that in SH-SY5Y cells. Differentiated SH-SY5Y cells were more sensitive to the effects of the anticonvulsants than undifferentiated SH-SY5Y cells. The results suggest that, the cell lines are promising neural models for the evaluation of drug side effects due to disturbances in glucose uptake.

• Authors: Marika Mannerström, Hanna Tähti
• Journal: Toxicology letters (Toxicol Lett) Vol. 151 Issue 1 Pg. 87-97 (Jun 15 2004) ISSN: 0378-4274 [Print] Netherlands
• PMID: 15177644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Antidepressive Agents
• Antimanic Agents
• Monoamine Oxidase Inhibitors
• Monosaccharide Transport Proteins
• 3-O-Methylglucose
• Amitriptyline
• Selegiline
• Carbamazepine
• Phenytoin

Topics

• 3-O-Methylglucose (metabolism, pharmacokinetics)
• Amitriptyline (pharmacology)
• Anticonvulsants (pharmacology)
• Antidepressive Agents (pharmacology)
• Antimanic Agents
• Carbamazepine (pharmacology)
• Cell Line, Tumor
• Humans
• Immunohistochemistry
• Monoamine Oxidase Inhibitors (pharmacology)
• Monosaccharide Transport Proteins (metabolism)
• Neuroglia (drug effects, metabolism)
• Neurons (drug effects, metabolism)
• Phenytoin (pharmacology)
• Selegiline (pharmacology)