Clarification of Intracellular Signal Transductions in Nifedipine-Reactive Human Gingival Fibroblasts

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In order to clarify the mechanism of gingival overgrowth caused by calcium channel blockers, we have studied cellular responses in human gingival fibroblasts (hGFs) originated from nifedipine non-reactive patient (nifedipine non-responder, NIFn) and nifedipine reactive patient (nifedipine responder, NIFr).1. Effect of nifedipine on protein phosphorylationThe present study was undertaken to identify the phosphorylated protein treated with bradykinin, thapsigargin, IL-1α, or nifedipine (NIF). NIF greatly stimulated the phospholylation specifically at 35 kDa protein in hGFs. The p38 phosphorylation caused by anisomycin was greater in NIFn than that of NIFr. Because of the capability of p38 inhibiting the cell cycle, it might be possible that cell proliferation of NIFr is greater than that of NIFn.2. Effect of non-steroidal anti-inflammatory drugs (NSAIDs) on intracellular pH (pHi) and intracellular Ca^<2+> concentration ([Ca^<2+>]i)We investigated the effects of stimulants (bradykinin, histamine, thapsigargin, cyclopiazonic acid) and NSAIDs on pHi in hGFs. All of stimulants and NSAIDs lowered pHi in hGFs and Tenidap and diclofenac Na greatly induced changes in pHi. Tenidap and mefenamic acid decreased the influx of extracellular [Ca^<2+>]i evoked by TG.These results indicate the possibility that Tenidap, diclofenac Na and mefenamic acid depress gingival overgrowth.