Effects of phenobarbital and phenytoin on cortical glial cells in culture.

Studies were undertaken to determine the effects of 7-day phenobarbital and phenytoin exposure on 14-day-old glial cell cultures of fetal murine cortex. Biochemical markers monitored were Ro5-4684-displaceable 3H-flunitrazepam binding, 3H-beta-alanine uptake, glutamine synthetase activity, and protein content. Phenobarbital concentrations were 30, 60, and 120 micrograms/ml and phenytoin concentrations 15, 30, 60 micrograms/ml. There were no discernible phase microscopic changes at any concentration of either drug. Phenobarbital produced no significant changes in the biochemical measures monitored. Exposure to phenytoin produced no biochemical changes at 15 micrograms/ml, but did produce significant changes at 30 and 60 micrograms/ml. There was an increase in Ro5-4684-displaceable 3H-flunitrazepam binding signifying increased binding or an increase in the number of binding sites and perhaps an increased population of glial cells although, the unchanged protein content suggests that the number of glial cells was not increased. There was a decrease with 30 and 60 micrograms/ml phenytoin of 3H-beta-alanine uptake suggesting interference with normal membrane transport of this compound. The latter effect may well mirror changes in GABA uptake in glial cells in the presence of phenytoin.