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

为了阐明钙通道阻滞剂引起牙龈过度生长的机制，我们研究了硝苯地平无反应患者（nifedipine non-responder, NIFn）和硝苯地平反应患者（nifedipine responder, NIFr）的人牙龈成纤维细胞（hGFs）的细胞反应。硝苯地平对蛋白磷酸化的影响本研究旨在鉴定缓激肽、thapsigargin、IL-1α或硝苯地平（NIF）处理后磷酸化的蛋白。NIF极大地刺激了hGFs中35 kDa蛋白的磷酸化。大霉素引起的p38磷酸化在NIFn中比在NIFr中更明显。由于p38具有抑制细胞周期的能力，NIFr的细胞增殖能力可能大于NIFn.2。非甾体抗炎药（NSAIDs）对hGFs细胞内pH （pHi）和细胞内Ca^<2+>浓度的影响（[Ca^<2+>]i）我们研究了兴奋剂（缓激肽、组胺、thapsigargin、环吡唑酸）和非甾体抗炎药对hGFs细胞内pHi的影响。所有兴奋剂和非甾体抗炎药均降低hGFs的pHi， Tenidap和双氯芬酸钠显著诱导pHi的变化。Tenidap和甲氧胺酸降低了TG引起的胞外[Ca^<2+>]i的内流。这些结果提示替尼达、双氯芬酸钠和甲氧胺酸可能抑制牙龈过度生长。

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.