Takezono Yasuhide, Joh Takashi, Oshima Tadayuki, Suzuki Hideo, Seno Kyoji, Yokoyama Yoshifumi, Alexander J Steven, Itoh Makoto
Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
J Lab Clin Med. 2004 Jan;143(1):52-8. doi: 10.1016/j.lab.2003.09.004.
Regulation of gastric epithelial permeability is important in the protection of the gastric mucosa from secreted acid. However, the mechanism(s) for this regulation in gastric mucus cells remains unknown. In this study, we evaluated gastric epithelial-cell permeability in response to acid exposure by monitoring trans-epithelial electrical resistance (TEER) and paracellular permeability with carbon 14-labeled mannitol. We also examined the role of prostaglandins on gastric epithelial permeability. Rat gastric epithelial cells (RGM-1) were plated on 8-microm-pore tissue-culture inserts. Cells were exposed to solutions of differing pH (3-7.4), with and without the nonsteroidal antiinflammatory drug (NSAID) indomethacin (10(-7) mol/L), for 60 to 120 minutes. Transepithelial permeability was measured on the basis of TEER and the diffusion rate of [(14)C]mannitol. Prostaglandin E(2) (PGE(2)) was administered in some experiments with NSAIDs. After acid exposure (pH 3.0-5.0), TEER rapidly and significantly increased, peaking in 5 minutes. Diffusion of [(14)C]mannitol was blocked during the period when TEER increased. Pretreatment with the cyclooxygenase (COX) inhibitor indomethacin blocked the rapid acid-induced increase in TEER. A specific COX-2 inhibitor had no effect on this rapid increase in TEER. The blockade by indomethacin was eliminated by the addition of PGE(2). These findings suggest that when gastric-surface mucus cells are exposed to acid, gastric epithelial permeability decreases rapidly to inhibit acid back-diffusion. Prostaglandins play an important role in this protective response to acid exposure. COX inhibitors such as indomethacin may inhibit the regulation of epithelial permeability by reducing the concentration of PGE(2).
胃上皮通透性的调节对于保护胃黏膜免受分泌酸的侵害至关重要。然而，胃黏液细胞中这种调节的机制仍然未知。在本研究中，我们通过监测跨上皮电阻（TEER）和用碳14标记的甘露醇检测细胞旁通透性，评估了胃上皮细胞对酸暴露的反应。我们还研究了前列腺素在胃上皮通透性中的作用。将大鼠胃上皮细胞（RGM-1）接种在8微米孔径的组织培养插入物上。细胞暴露于不同pH值（3 - 7.4）的溶液中，有或没有非甾体抗炎药（NSAID）吲哚美辛（10^(-7) mol/L），持续60至120分钟。基于TEER和[14C]甘露醇的扩散速率测量跨上皮通透性。在一些使用NSAIDs的实验中给予前列腺素E2（PGE2）。酸暴露（pH 3.0 - 5.0）后，TEER迅速且显著增加，在5分钟时达到峰值。在TEER增加期间，[14C]甘露醇的扩散被阻断。用环氧化酶（COX）抑制剂吲哚美辛预处理可阻断酸诱导的TEER快速增加。一种特异性COX-2抑制剂对TEER的这种快速增加没有影响。加入PGE2可消除吲哚美辛的阻断作用。这些发现表明，当胃表面黏液细胞暴露于酸时，胃上皮通透性迅速降低以抑制酸的反向扩散。前列腺素在这种对酸暴露的保护反应中起重要作用。诸如吲哚美辛之类的COX抑制剂可能通过降低PGE2的浓度来抑制上皮通透性的调节。
