Rebamipide, an anti-ulcerative drug, inhibits induction of salivary dysfunction by benzodiazepines
Rebamipide, an anti-ulcerative drug, inhibits induction of salivary dysfunction by benzodiazepines
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瑞巴派特是一种抗溃疡药，可抑制苯二氮卓类药物引起的唾液功能障碍
DOI：
10.1111/odi.12642
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发表时间：
2017
期刊：
影响因子：
3.8
通讯作者：
Kawaguchi M.
中科院分区：
文献类型：
--
作者：
Ogane M;Okubo M;Yoshikawa M;Shinomiya T;Tsukagoshi E;Kawaguchi M.
目的本研究的目的是确定瑞巴派特，一种抗胃溃疡剂，是否改善苯二氮卓类诱导的大鼠腮腺（PG）和颌下腺（SMG）的唾液减少。用溶于生理盐水的毛果芸香碱刺激后每15分钟给药一次，持续1小时，并以1 mg kg-1腹腔内给药。地西泮（DZP）以0.2 mg kg-1的剂量每日两次腹腔内给药，持续7天。瑞巴派特以10、20、30或100 mg kg− 1与DZP同时给药，以确定其对唾液减少的影响。瑞巴派特对离体腮腺腺泡细胞内钙离子（[Ca 2 +]i）运动的影响进行了分析，使用Fluo 4，一种荧光染料用于检测Ca 2 +. ResultsRepetitive-administration的DZP减少PG和SMG的唾液分泌。这种抑制作用被瑞巴派特减弱。预先给予DZP（10− 6 M）可显著抑制卡巴胆碱（10− 7 M）诱导的[Ca 2 +]i升高。与瑞巴派特（5 × 10 - 4 M）联合使用可改善这种抑制作用。结论这一发现表明，瑞巴派特通过阻止DZP诱导的对[Ca 2 +]i增加的抑制来削弱DZP对唾液分泌的下调作用。
ObjectivesThe purpose of this study was to determine whether rebamipide, an antistomach ulcer agent, ameliorated benzodiazepine‐induced hyposalivation in rat parotid gland (PG) and submandibular gland (SMG).MethodsSaliva was collected from PG and SMG through a capillary cannula inserted into the parotid duct and sublingual papillae, respectively, every 15 min for 1 h after stimulation with pilocarpine dissolved in physiological saline and intraperitoneally administered at 1 mg kg−1. Diazepam (DZP) was administered intraperitoneally at a dose of 0.2 mg kg−1twice daily for 7 days. Rebamipide was administered at 10, 20, 30, or 100 mg kg−1concomitantly with DZP to determine its effect on hyposalivation. The effect of rebamipide on movement of intracellular calcium ([Ca2+]i) in isolated parotid acinar cells was analyzed using Fluo4, a fluorescent dye used to detect Ca2+.ResultsRepetitive administration of DZP decreased salivary secretion in PG and SMG. This inhibitory effect was weakened by administration of rebamipide. Prior administration of DZP (10−6M) significantly suppressed carbachol (10−7M)‐induced increase in [Ca2+]i. This inhibitory effect was ameliorated by combined use with rebamipide (5 × 10−4M).ConclusionThis findings suggest that rebamipide weakens the downregulatory effect of DZP on salivary secretion by preventing DZP‐induced suppression of increase in [Ca2+]i.