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(NIFn)和硝苯地平反应者(NIFr)来源的人牙龈成纤维细胞(HGFs)的细胞反应。硝苯地平对蛋白质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)处理的磷酸化蛋白质。NIF能显著促进HGFs中35 kDa蛋白的磷酸化。NIFn组p38蛋白的磷酸化程度明显高于NIFr组。结论：1.由于p38对细胞周期的抑制作用，NIFr的细胞增殖作用可能大于NIFn1。非甾体抗炎药(NSAIDs)对细胞内pH(Phi)和细胞内钙离子浓度([Ca^&lt；2+&gt；]i)的影响我们观察了刺激剂(缓激肽、组胺、塔西林、环匹阿糖酸)和NSAIDs对HGFp i的影响。所有刺激剂和非甾体抗炎药均可降低HGFs的pH，替尼达普和双氯芬酸钠均可引起PHi的明显改变。替尼达普和甲芬那酸均能降低TG引起的细胞外[Ca~(2+)]i内流，提示替尼达普、双氯芬酸钠和甲芬那酸可能抑制牙周组织的过度生长。

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.