Background:The
mechanism concerning gingival overgrowth as a side effect of phenytoin, a
therapeutic drug for epilepsy has been still unclear. As one of mechanisms, by
measuring the intracellular calcium concentration ([Ca2+]i)
of the gingival fibroblasts, it has been advocated that there is relationship
between gingival overgrowth and phenytoin-induced alterations in the [Ca2+]i
in gingival fibroblasts. To confirm that phenytoin elevates the [Ca2+]i,
and if so, to find out its mode of action.Methods: The [Ca2+]i was measured with the Ca2+-sensitive
fluorescent dye fura-2/AM. Cells were soaked in a flexiperm chamber and
perfused by a saline. Drugs at appropriate concentrations were added to the perfusate. Results:Phenytoin concentration-dependently elevated the [Ca2+]i.
NPS2390, a calcium-sensing receptor (CaSR)
blocker, significantly suppressed the phenytoin-induced [Ca2+]i
elevation. U73122, a phospholipase C (PLC) inhibitor, inihibited the
phenytoin-induced [Ca2+]i elevation. TMB-8, a blocker of inositol
triphophate (IP3) receptors in ER, significantly depressed the
phenytoin-induced [Ca
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