修回日期: 2004-02-09
接受日期: 2004-02-26
在线出版日期: 2004-06-15
胃黏膜壁细胞是胃腺内一种重要的分泌细胞, 具有泌酸、产生内因子及调节胃内酸碱水平等作用, 其中尤以泌酸功能最为重要:一方面, 组胺、乙酰胆碱(Ach)和胃泌素等促分泌因子可通过各种途径调节盐酸分泌; 另一方面, 壁细胞泌酸也与其特征性的形态学改变相关联. 近年来, 又发现壁细胞还参与调控胃黏膜细胞的增生和分化. 目前, 对胃壁细胞酸分泌的调节机制及其影响因素、在泌酸过程中的结构变化乃至其超微结构、电生理和对胃黏膜上皮分化调控等方面的研究均取得长足进步.
引文著录: 徐远溪, 王志荣, 陈锡美. 胃黏膜壁细胞研究进展. 世界华人消化杂志 2004; 12(6): 1397-1401
Revised: February 9, 2004
Accepted: February 26, 2004
Published online: June 15, 2004
N/A
- Citation: N/A. N/A. Shijie Huaren Xiaohua Zazhi 2004; 12(6): 1397-1401
- URL: https://www.wjgnet.com/1009-3079/full/v12/i6/1397.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v12.i6.1397
胃黏膜壁细胞, 亦称泌酸细胞, 位于胃腺颈部, 占胃上皮细胞总数的30%. 其主要功能为分泌盐酸, 对胃内酸碱平衡的维持有重要作用. 胃壁细胞有逆250万倍梯度浓度分泌H+的能力, 这是H+-K+ -ATP酶(质子泵)作用的结果, 又与壁细胞特征性形态学改变相关联. 组胺、Ach等促分泌因子通过神经、旁分泌和内分泌途径, 介导调节盐酸的分泌, 除通过激活环腺苷酸(cAMP), 增加Ca2+内流来刺激泌酸外, 还伴有离子通道的调节[1-5]. 随着细胞生物学、分子生物学和各种显微技术的完善, 壁细胞对胃黏膜增生分化的直接或间接调控作用日显重要. 对壁细胞上述功能特点的研究, 既有助于壁细胞的体外分离和培养, 又有助于阐明消化性溃疡、胃酸缺乏症等疾病的发病机制及相关药物的研发.
胃壁细胞属高度特异的终末分化细胞, 不能进行传代培养, 且在整个生长过程中, 每日死亡率达5-10%. 因此, 建立体外培养壁细胞的方法十分必要.
陈蕾et al[6-7]选用♂SD大鼠, 剖腹取胃后, 在胃底作一1.0 cm小切口. 将胃翻转, 使胃黏膜面朝外而浆膜面向内, 在胃幽门部结扎, 并经胃底部切口用注射器将链霉蛋白(Pronase)注入胃袋, 注满为止. 待充分水浴消化后, 离心、洗涤沉淀并制成细胞悬液, 将该悬液置于离心管最上层再次离心, 所得上悬液层即为壁细胞. 分离后的壁细胞用PBS液制备成细胞悬液后接种到培养液中, 放入培养箱30 min以去除成纤维细胞, 最后把提纯的壁细胞接种至鼠尾胶原包被的盖玻片上. 这种方法不但能使Pronase局限于浆膜层, 减轻对壁细胞的损伤, 而且黏膜面朝向浴液, 供氧充分, 无刮取黏膜时对细胞造成的机械损伤, 利于细胞的成活. 经上述方法培养, 壁细胞纯度可达80%, 成活率高达95%以上.
鉴于壁细胞无法传代且分离过程繁琐, Carmosino et al[8]培养的人胃壁细胞HGT-1弥补了以上不足. HGT-1具有和体内壁细胞类似的生理学特征: 能够在组胺刺激下分泌H+; 用100 mmoL奥美拉唑(Omepazole)处理后能够抑制组胺诱导的胞膜顶端泌酸作用; 在HGT-1中检测到组胺和Na+/H+交换器, 这与在胃上皮细胞和原代培养的壁细胞中发现的NHE4的功能性表达相一致. 因此, HGT-1细胞系或许能作为研究壁细胞泌酸调节的替代模型.
1.2.1 rab家族: rabGTP酶是GTP结合蛋白超家族中的一种, 已被证明与壁细胞胞内动力学和泡囊膜运输有关. 壁细胞内有一系列rabGTP酶, 分子量20-25 kD, 含有保守性鸟嘌呤核苷酸序列和疏水性基元. 某些特殊的rab还与胞内分泌结构有关, 并是膜动力学的重要调节器, 其中以rab11较为特殊[9-15]. rab11在壁细胞中大量表达[16-19]. 在兔胃壁细胞微粒体中rab11的主要存在形式是rab11a, 与H+-K+-ATP酶共存于管状泡囊膜上, 用化学计量法推算每六个质子泵含有一个rab11a. 在壁细胞受刺激时, rab11a和质子泵一起重分布, 即从管状泡囊移至分泌膜, 对质子泵-膜补充过程有一定作用. 腺病毒感染细胞后产生的rab11a隐性突变型rab11N124I则起相反作用: 在未受感染的细胞中, 质子泵在胞质内大范围分布, 在受刺激时质子泵从胞质中被清除并向顶端膜迁移; 而在表达rab11N124I的细胞, 质子泵在受刺激时仍保持其在静息状态时的位置, 这种现象在用四环素后会被遏制, 阻止了rab11突变型的表达. 由此, Duman et al[20-21]证实了对rab11的干扰与壁细胞泌酸调控存在联系.
1.2.2 包涵素家族: 包涵素(Clathrin)是泡囊外衣蛋白中最具特征的一个家族, 存在于富含质子泵的管状泡囊上, 他在壁细胞中的主要作用有: 对胞内物质加以选择, 使其聚集, 并作为将选择后物质运送至邻近泡囊的途径; 聚集其他各类蛋白质, 使胞膜变形成为运输泡囊或管道. 上述作用表明包涵素可能与质子泵在分泌膜的恢复以及管状泡囊的生物起源和持续再构建有关[22-30].
1.3.1 壁细胞超微结构分析: Sawaguchi et al[31-32]设计的高压冷冻保存原代培养细胞可观察到极佳的壁细胞超微结构. 将分离的壁细胞在覆盖有Matrigel胶的铝盘上培养, 随后进行高压冷冻保存. 细胞的超微结构如高尔基体、微粒体等与传统化学固定法相比保存得更好, 微绒毛和胞质中的肌纤维细丝也能清晰显示. 运用上述方法, 可探讨壁细胞在消化性溃疡发病机制中的形态学改变. 经胃镜取材组织病理学确诊的消化性溃疡患者和正常人选择同一地区、组织作对照研究[33-35]. 经体视学分析及超微结构观察, 结果发现两组间壁细胞平均剖面直径、平均剖面积、平均体积、体积密度和数量均无显著差异. 电镜下胃溃疡患者壁细胞内微管泡系统少且散乱, 线粒体稀疏; 十二指肠溃疡患者胞内则有大量微管泡系统, 线粒体增多明显; 对照组微管泡系统丰富, 线粒体嵴呈板状. 由此可见, 十二指肠溃疡患者的高胃酸状态实与壁细胞泌酸功能的增强有关, 而非壁细胞总数增加; 与正常人相比胃溃疡患者则无明显变化.
1.3.2 壁细胞氯离子通道研究: 研究表明, 壁细胞氯离子通道有三种重要生理学特点: (1)在控制膜电位过程中的管家作用; (2)NO/cGMP蛋白激酶途径介导的氯离子通道的开放能防御乙醇诱导的损伤; (3)可被GTP结合蛋白介导的产生于胞内的超氧阴离子所抑制[36-40].
壁细胞共有两种氯离子通道, 即分泌膜氯离子通道和基底膜氯离子通道. 通常采用细胞贴附式即膜内面向外式和全细胞记录法来研究这两种通道. 前者在给予组胺10-4 moL/L后, 可记录到一种电压依赖性氯离子电流. 该通道随刺激电压绝对值增加开放频率亦增高, 其改变呈不对称抛物线型, 该通道还参与胃酸分泌, 对Na+、K+通透性极低. 全细胞记录法则用来观察基底膜氯离子通道, 其电流-电压曲线为过原点的直线, 在细胞内外等氯离子浓度时无整流特性, 基底膜电位在维持膜稳定中起重要作用. 由于细胞外液酸化可抑制氯电流, 而具细胞保护作用的PGE2可增强该电流, 提示此通道与细胞保护机制有关.
2.1.1 受体机制: 已知壁细胞底侧膜上有胃泌素、Ach和组胺三种激动型受体, 他们与配体结合后, 能激活胞内第二信使, 使后者浓度发生改变, 进而激活蛋白激酶; 同时胞内Ca2+亦增加, 最终经放大效应促进胃酸分泌. 胃泌素和Ach受体引起泌酸的机制与受体后信号传递有关, 即当胃泌素和Ach与各自受体结合后导致膜内分子水平变化. 胃泌素使壁细胞膜磷脂水解, 由磷脂酰二磷酸肌醇(PIP2)分解成三磷酸肌醇(IP3)和二酰甘油(DG). IP3分1、2、3三种亚型, 广泛分布于胞液和管状泡囊的微粒体中, 他通过促进胞内钙库释放Ca2+, 增加胞内游离Ca2+浓度. 在IP3诱导Ca2+由胞外入胞的同时, 胃泌素又能刺激IP3, 使其含量迅速上升且持续增加, 故具有双相动力学效应[41]. DG是钙离子依赖蛋白激酶(PKC)特异性激动剂, 使PKC从胞质移至质膜, Ach也能使PKC活化, 诱导胞内Ca2+浓度升高[42-43]. 不管何种受体途径, 最终均启动Ca2+信号系统即Ca2+-磷脂依赖性激酶途径, 激活质子泵促进酸分泌[44].
组胺受体与其配体结合后, 通过cAMP-PKA途径起作用. 组胺和胆碱能受体M3亚型结合后, 使AMP在酰苷酸环化酶(AC)的作用下变为cAMP, cAMP进而发挥两大作用: 活化钙泵, 即使在cAMP信号减弱时壁细胞基底膜仍可有Ca2+浓度升高, 而期间产生的能量为质子泵泌H+提供动力; 活化cAMP依赖蛋白激酶(PKA), 后者进而促使碳酸苷酶活化, 形成碳酸并离解H+或使蛋白质磷酸化, 直接激活质子泵促进酸分泌[45].
2.1.2 生理学机制: 壁细胞泌酸通过含质子泵的泡囊运动来控制, 而泡囊之所以能膨胀收缩自如, 主要依赖于壁细胞内的肌动蛋白(actin). 壁细胞中90%的肌动蛋白是F-肌动蛋白. 在静息态壁细胞中, F-肌动蛋白和G-肌动蛋白保持稳定的F/G比例关系, 该比例不因壁细胞被激活而发生改变. F-肌动蛋白聚合成多聚体后, 形成细肌丝主干, 从而影响和控制蛋白质间的相互作用, 控制壁细胞顶端膜微绒毛的伸缩, 达到控制泡囊运动、使质子泵迁移的目的. 有学者从红海海绵中提取毒素LatA(Latrunculins A), 他可以抑制上述作用, 但并不直接抑制F-肌动蛋白的聚合, 而主要针对游离肌动蛋白单体, 将其从多聚化位点分隔开或与G-肌动蛋白按1:1比例结合成复合体阻止肌丝形成, 但不影响肌动蛋白更新速率[46-50].
2.1.3 膜运输机制: 壁细胞受促分泌因素刺激时会发生形态学上的变化, 以及酶的位置、活性和离子通道都会发生改变. 原来萎缩的分泌小管发生膨胀, 同时含质子泵的管状泡囊消失, 微绒毛内的肌动蛋白细丝介导分泌小管和管状泡囊的融合, 质子泵被转移至膜顶端, H+泵出和K+交换, 从而达到分泌盐酸的目的, 这就是经典的膜运输(循环)学说.
所谓膜运输学说, 其本质是壁细胞酸分泌过程中分泌膜上受促分泌因素调节的质子泵的再循环. 在泌酸过程中质子泵的运输及分泌膜的重塑与泡囊转运机制和细胞骨架的协调作用有关. 壁细胞被激活时, 分泌膜对K+有高通透性, 使K+能经分泌膜再循环, 同时也为H+-K+-ATP酶提供胞外K+; 在未激活或静息态壁细胞中, 质子泵滞留在胞液内的管状泡囊膜上, 该膜对K+通透性较低, 这可避免静息态时产生多余的酸. 在受刺激后, 壁细胞分泌膜表面积扩大5-10倍, 而扩大的面积在数量上相当于胞液中管状泡囊缩小时的面积. Hirst et al[51-53]发现壁细胞内盐酸积聚后, 萎陷或卷曲的管状泡囊会被吞噬, 从而使分泌膜面积相应增长, 被内吞的管状泡囊上富含的质子泵会融入分泌膜, 泌H+后又离开分泌膜, 回到胞质中转归为静息态. 近来对壁细胞的分离培养为泌酸的再循环理论和渗透性膨胀提供了解释. 在培养基中, 壁细胞丧失或改变其极性, 分泌膜被内吞形成一系列包涵体(VACs), 而底侧膜则成为环绕于胞质的膜. 在非分泌壁细胞中, F-肌动蛋白位于VACs和底侧膜上, 而质子泵遍布于胞质内的管状泡囊上. 受刺激时, 质子泵同F-肌动蛋白一起定居于VACs上. 即便这种渗透性吞饮作用为质子泵阻滞剂(PPI)所阻断, 壁细胞仍然会出现胞内质子泵的清除并向VACs转移. 以上表明在泌酸的膜运输理论中, 富含质子泵的管状泡囊迁移并播散至分泌膜, 而非后者向胞质内的延伸[54-55].
Neu et al[56-59]发现在幽门螺旋杆菌(Hp)引起的慢性胃炎过程中, 以TNF-α为主的细胞因子与壁细胞的程序化死亡有关. 在大鼠壁细胞的培养液中, 加入10 ng/mL浓度的TNF-α可诱导大鼠胃壁细胞的凋亡, 且凋亡速度增加2.6倍. TNF-α的促凋亡作用可为各类NF-κB抑制剂、NOS抑制剂所终止. 对凋亡细胞下游信号传导通路的检测发现TNF-α能介导诱导型一氧化氮合酶(iNOS)的表达, TNF-α对壁细胞的作用是导致Hp感染后慢性胃黏膜萎缩和胃酸缺乏的原因之一. 与之相反, 间叶转录因子Fkh6则是壁细胞衍变分化所必需的, 含此因子的壁细胞具有分化良好的胞内管道和线粒体, 对泌酸刺激不敏感. Fkh6在壁细胞通过上皮－间叶交互作用而分化的过程中起重要作用[60-61].
胃黏膜泌酸的结构功能单位为胃小凹或胃陷窝(pit region), 内含壁细胞、主细胞、内分泌细胞和隐窝细胞等. 各类细胞更新速率长短不一, 如壁细胞2 mo, 主细胞为200 d. 以壁细胞为调控因素, 观察其他各类细胞的更新代谢情况, 已成为新的研究方向. 加工前体蛋白质的费林蛋白质酶(furin)位于陷窝区的上皮细胞, 他能将多种生长和分化相关蛋白转化成活性形式. Kamimuraet al[62-65]用免疫染色的方法检测鼠胃黏膜细胞, 发现陷窝区内的壁细胞furin呈阳性表达, 无转化生长因子a(TGF-a)着色, 但为TGF-a+的表面黏膜细胞(GSM)包绕. TGF-a以旁分泌形式从壁细胞分泌, 当GSM接触壁细胞时, 二者会通过细胞间相互作用交换重要信号, 前者可出现DNA合成, 表明TGF-a从GSM传导至壁细胞后, 再刺激GSM生长. 壁细胞在维持黏膜增生中起轴心作用, 在将壁细胞剔除后鼠黏膜有萎缩性胃炎的表现. 总之, 壁细胞通过furin介导, 以TGF-a和EGFR作用于黏膜上皮细胞, 促其更新, 从而维持隐窝区的细胞结构层次. Stewart et al[66]在壁细胞H+-K+-ATP酶b亚单位调控序列的控制下, 对携带有温度敏感突变型SV40 T抗原(SV40tsA58)的转基因小鼠进行传代, 建立了三种H+-K+-ATP酶b-tsA58系小鼠: 218、224和228. 三系小鼠均出现胃黏膜肥厚, 上皮细胞增生, 并在37 ℃ SV40 T抗原部分被激活. 免疫荧光及电镜显示在218、224两系中成熟壁细胞和酶原细胞均缺失, 胃腺中一种小型未分化细胞是主要细胞类型; 而在228系中可见部分成熟壁细胞、比例不断增长的未分化细胞和很少见的前壁细胞, 33 ℃为最适培养温度. SV40T抗原基因转染的胃上皮细胞也能在培养基中存活6 wk以上, 并且当温度升至39 ℃时, 会出现类似干细胞的分化特性, 有转化为各类胃黏膜细胞的倾向. 因此, 该品系小鼠的建立提示壁细胞携带的SV40tsA58具有诱导自身和上皮细胞分化的作用. H+-K+-ATP酶是壁细胞正常生长所必需的, 在壁细胞参与胃黏膜细胞生长调控方面也起重要作用. 缺乏H+-K+-ATP酶b亚单位的小鼠, 胃泌素过量产生, 每个胃小区未成熟细胞数增长3.1倍, 胃黏膜上皮增生肥厚, 壁细胞分泌膜出现异常而持续泌酸[67], 而且在最适培养温度下壁细胞会有H+-K+-ATP酶b亚单位急剧增加并出现分化趋势. 这些证据表明H+-K+-ATP酶的存在保证了内环境的稳定, 限制了未成熟细胞向终末态上皮细胞转化的数量, 并可使二者间比例关系保持恒定.
总之, 胃壁细胞作为胃内泌酸的关键细胞, 与胃内酸碱度的维持、离子通道研究及神经体液的相互调节都密切相关. 在泌酸过程中, 壁细胞通过其表面的各类受体及胞内一系列形态学改变来完成. 离体壁细胞培养成功, 对于其超微结构的深入研究, 有益于阐明其与消化疾病发病机制的关系. 同时, 壁细胞调控胃上皮细胞增生分化为胃黏膜干细胞研究提供了思路, 如肠型早期胃癌中的局灶性壁细胞分化等[68]. 当然, 有关壁细胞的起源, 即壁细胞是否源于H+-K+-ATP酶基因从远古微生物向高等生物的衍变[69-70]; 泌酸时壁细胞胞质中线粒体构成网状组织, 该组织对线粒体功能有何意义等问题仍亟待解决.
| 1. | Chen D, Zhao CM, Håkanson R, Samuelson LC, Rehfeld JF, Friis-Hansen L. Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice. Gastroenterology. 2004;126:476-487. [PubMed] [DOI] |
| 2. | Okabe S, Fujishita T, Jinbo K. [New target for the inhibitors of gastric acid secretion. Inhibition of myosin and actin activities via the apical membrane of parietal cells in dogs]. Nihon Yakurigaku Zasshi. 2003;122 Suppl:74P-77P. [PubMed] |
| 3. | Sawaguchi A, McDonald KL, Forte JG. High-pressure freezing of isolated gastric glands provides new insight into the fine structure and subcellular localization of H+/K+-ATPase in gastric parietal cells. J Histochem Cytochem. 2004;52:77-86. [PubMed] [DOI] |
| 4. | Malinowska DH, Sherry AM, Tewari KP, Cuppoletti J. Gastric parietal cell secretory membrane contains PKA- and acid-activated Kir2.1 K+ channels. Am J Physiol Cell Physiol. 2004;286:C495-C506. [PubMed] [DOI] |
| 5. | Sachs G. Physiology of the parietal cell and therapeutic implications. Pharmacotherapy. 2003;23:68S-73S. [PubMed] [DOI] |
| 8. | Carmosino M, Procino G, Casavola V, Svelto M, Valenti G. The cultured human gastric cells HGT-1 express the principal transporters involved in acid secretion. Pflugers Arch. 2000;440:871-880. [PubMed] [DOI] |
| 9. | Goldenring JR, Tang LH, Modlin IM. Small GTP-binding proteins in parietal cells: candidate modulators of parietal cell membrane dynamics. Yale J Biol Med. 1992;65:597-605. [PubMed] |
| 10. | Thériault C, Rochdi MD, Parent JL. Role of the Rab11-associated intracellular pool of receptors formed by constitutive endocytosis of the beta isoform of the thromboxane A2 receptor (TP beta). Biochemistry. 2004;43:5600-5607. [PubMed] [DOI] |
| 11. | Fan GH, Lapierre LA, Goldenring JR, Sai J, Richmond A. Rab11-family interacting protein 2 and myosin Vb are required for CXCR2 recycling and receptor-mediated chemotaxis. Mol Biol Cell. 2004;15:2456-2469. [PubMed] [DOI] |
| 12. | Bartz R, Benzing C, Ullrich O. Reconstitution of vesicular transport to Rab11-positive recycling endosomes in vitro. Biochem Biophys Res Commun. 2003;312:663-669. [PubMed] [DOI] |
| 13. | Pelissier A, Chauvin JP, Lecuit T. Trafficking through Rab11 endosomes is required for cellularization during Drosophila embryogenesis. Curr Biol. 2003;13:1848-1857. [PubMed] [DOI] |
| 14. | McGugan GC Jr, Temesvari LA. Characterization of a Rab11-like GTPase, EhRab11, of Entamoeba histolytica. Mol Biochem Parasitol. 2003;129:137-146. [PubMed] [DOI] |
| 15. | Wallace DM, Lindsay AJ, Hendrick AG, McCaffrey MW. Rab11-FIP4 interacts with Rab11 in a GTP-dependent manner and its overexpression condenses the Rab11 positive compartment in HeLa cells. Biochem Biophys Res Commun. 2002;299:770-779. [PubMed] [DOI] |
| 16. | Calhoun BC, Goldenring JR. Rab proteins in gastric parietal cells: evidence for the membrane recycling hypothesis. Yale J Biol Med. 1996;69:1-8. [PubMed] |
| 17. | Meyers JM, Prekeris R. Formation of mutually exclusive Rab11 complexes with members of the family of Rab11-interacting proteins regulates Rab11 endocytic targeting and function. J Biol Chem. 2002;277:49003-49010. [PubMed] [DOI] |
| 18. | Lindsay AJ, Hendrick AG, Cantalupo G, Senic-Matuglia F, Goud B, Bucci C, McCaffrey MW. Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein. J Biol Chem. 2002;277:12190-12199. [PubMed] [DOI] |
| 19. | Pasqualato S, Senic-Matuglia F, Renault L, Goud B, Salamero J, Cherfils J. The structural GDP/GTP cycle of Rab11 reveals a novel interface involved in the dynamics of recycling endosomes. J Biol Chem. 2004;279:11480-11488. [PubMed] [DOI] |
| 20. | Duman JG, Tyagarajan K, Kolsi MS, Moore HP, Forte JG. Expression of rab11a N124I in gastric parietal cells inhibits stimulatory recruitment of the H+-K+-ATPase. Am J Physiol. 1999;277:C361-C372. [PubMed] |
| 21. | Agnew BJ, Duman JG, Watson CL, Coling DE, Forte JG. Cytological transformations associated with parietal cell stimulation: critical steps in the activation cascade. J Cell Sci. 1999;112:2639-2646. [PubMed] |
| 22. | Okamoto CT, Jeng YY. An immunologically distinct beta-adaptin on tubulovesicles of gastric oxyntic cells. Am J Physiol. 1998;275:C1323-C1329. [PubMed] |
| 23. | Bennett EM, Chen CY, Engqvist-Goldstein AE, Drubin DG, Brodsky FM. Clathrin hub expression dissociates the actin-binding protein Hip1R from coated pits and disrupts their alignment with the actin cytoskeleton. Traffic. 2001;2:851-858. [PubMed] [DOI] |
| 24. | Okamoto CT, Karam SM, Jeng YY, Forte JG, Goldenring JR. Identification of clathrin and clathrin adaptors on tubulovesicles of gastric acid secretory (oxyntic) cells. Am J Physiol. 1998;274:C1017-C1029. [PubMed] |
| 25. | Baig AH, Swords FM, Szaszák M, King PJ, Hunyady L, Clark AJ. Agonist activated adrenocorticotropin receptor internalizes via a clathrin-mediated G protein receptor kinase dependent mechanism. Endocr Res. 2002;28:281-289. [PubMed] [DOI] |
| 26. | Kalthoff C, Groos S, Kohl R, Mahrhold S, Ungewickell EJ. Clint: a novel clathrin-binding ENTH-domain protein at the Golgi. Mol Biol Cell. 2002;13:4060-4073. [PubMed] [DOI] |
| 27. | Chen CY, Reese ML, Hwang PK, Ota N, Agard D, Brodsky FM. Clathrin light and heavy chain interface: alpha-helix binding superhelix loops via critical tryptophans. EMBO J. 2002;21:6072-6082. [PubMed] [DOI] |
| 28. | Blanpied TA, Scott DB, Ehlers MD. Dynamics and regulation of clathrin coats at specialized endocytic zones of dendrites and spines. Neuron. 2002;36:435-449. [PubMed] [DOI] |
| 29. | Gall WE, Geething NC, Hua Z, Ingram MF, Liu K, Chen SI, Graham TR. Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo. Curr Biol. 2002;12:1623-1627. [PubMed] [DOI] |
| 30. | Rodionov DG, Höning S, Silye A, Kongsvik TL, von Figura K, Bakke O. Structural requirements for interactions between leucine-sorting signals and clathrin-associated adaptor protein complex AP3. J Biol Chem. 2002;277:47436-47443. [PubMed] [DOI] |
| 31. | Sawaguchi A, McDonald KL, Karvar S, Forte JG. A new approach for high-pressure freezing of primary culture cells: the fine structure and stimulation-associated transformation of cultured rabbit gastric parietal cells. J Microsc. 2002;208:158-166. [PubMed] [DOI] |
| 32. | Sawaguchi A, McDonald KL, Forte JG. High-pressure freezing of isolated gastric glands provides new insight into the fine structure and subcellular localization of H+/K+-ATPase in gastric parietal cells. J Histochem Cytochem. 2004;52:77-86. [PubMed] [DOI] |
| 35. | 李 玉梅, 邹 晓平, 李 兆申, 彭 贵勇, 湛 先保, 屠 振兴, 房 殿春, 许 国铭. 应激性溃疡时大鼠胃壁细胞功能及超微结构的动 态变化. 中国病理生理杂志. 2003;19:1058-1061. |
| 36. | Sakai H. [A cytoprotective chloride channel in gastric parietal cells]. Yakugaku Zasshi. 1999;119:584-596. [PubMed] [DOI] |
| 37. | Coelho RR, Souza EP, Soares PM, Meireles AV, Santos GC, Scarparo HC, Assreuy AM, Criddle DN. Effects of chloride channel blockers on hypotonicity-induced contractions of the rat trachea. Br J Pharmacol. 2004;141:367-373. [PubMed] [DOI] |
| 38. | Gong X, Linsdell P. Mutation-induced blocker permeability and multiion block of the CFTR chloride channel pore. J Gen Physiol. 2003;122:673-687. [PubMed] [DOI] |
| 39. | Steendahl J, Holstein-Rathlou NH, Sorensen CM, Salomonsson M. Effects of chloride channel blockers on rat renal vascular responses to angiotensin II and norepinephrine. Am J Physiol Renal Physiol. 2004;286:F323-F330. [PubMed] [DOI] |
| 40. | Bernucci L, Umaña F, Llanos P, Riquelme G. Large chloride channel from pre-eclamptic human placenta. Placenta. 2003;24:895-903. [PubMed] [DOI] |
| 41. | Muto Y, Nagao T, Yamada M, Mikoshiba K, Urushidani T. A proposed mechanism for the potentiation of cAMP-mediated acid secretion by carbachol. Am J Physiol Cell Physiol. 2001;280:C155-C165. [PubMed] |
| 42. | Pan QS, Fang ZP, Huang FJ. Identification, localization and morphology of APUD cells in gastroenteropancreatic system of stomach-containing teleosts. World J Gastroenterol. 2000;6:842-847. [PubMed] [DOI] |
| 43. | Faber ES, Sah P. Calcium-activated potassium channels: multiple contributions to neuronal function. Neuroscientist. 2003;9:181-194. [PubMed] [DOI] |
| 44. | Zeng N, Athmann C, Kang T, Lyu RM, Walsh JH, Ohning GV, Sachs G, Pisegna JR. PACAP type I receptor activation regulates ECL cells and gastric acid secretion. J Clin Invest. 1999;104:1383-1391. [PubMed] [DOI] |
| 45. | Athmann C, Zeng N, Scott DR, Sachs G. Regulation of parietal cell calcium signaling in gastric glands. Am J Physiol Gastrointest Liver Physiol. 2000;279:G1048-G1058. [PubMed] |
| 46. | Ammar DA, Nguyen PN, Forte JG. Functionally distinct pools of actin in secretory cells. Am J Physiol Cell Physiol. 2001;281:C407-C417. [PubMed] |
| 47. | Li C, Cheng Y, Gutmann DA, Mangoura D. Differential localization of the neurofibromatosis 1 (NF1) gene product, neurofibromin, with the F-actin or microtubule cytoskeleton during differentiation of telencephalic neurons. Brain Res Dev Brain Res. 2001;130:231-248. [PubMed] [DOI] |
| 48. | Cintio O, Adami R, Choquet D, Grazi E. On the elastic properties of tetramethylrhodamine F-actin. Biophys Chem. 2001;92:201-207. [PubMed] [DOI] |
| 49. | Orlova A, Galkin VE, VanLoock MS, Kim E, Shvetsov A, Reisler E, Egelman EH. Probing the structure of F-actin: cross-links constrain atomic models and modify actin dynamics. J Mol Biol. 2001;312:95-106. [PubMed] [DOI] |
| 50. | Jahraus A, Egeberg M, Hinner B, Habermann A, Sackman E, Pralle A, Faulstich H, Rybin V, Defacque H, Griffiths G. ATP-dependent membrane assembly of F-actin facilitates membrane fusion. Mol Biol Cell. 2001;12:155-170. [PubMed] [DOI] |
| 51. | Hirst BH. Parietal cell membrane trafficking. Focus on "Expression of rab11a N124I in gastric parietal cells inhibits stimulatory recruitment of the H+-K+-ATPase". Am J Physiol. 1999;277:C359-C360. [PubMed] |
| 52. | Watson RT, Kanzaki M, Pessin JE. Regulated membrane trafficking of the insulin-responsive glucose transporter 4 in adipocytes. Endocr Rev. 2004;25:177-204. [PubMed] [DOI] |
| 53. | Strickland LI, Burgess DR. Pathways for membrane trafficking during cytokinesis. Trends Cell Biol. 2004;14:115-118. [PubMed] [DOI] |
| 54. | Okamoto CT, Forte JG. Vesicular trafficking machinery, the actin cytoskeleton, and H+-K+-ATPase recycling in the gastric parietal cell. J Physiol. 2001;532:287-296. [PubMed] [DOI] |
| 55. | Okamoto CT, Li R, Zhang Z, Jeng YY, Chew CS. Regulation of protein and vesicle trafficking at the apical membrane of epithelial cells. J Control Release. 2002;78:35-41. [PubMed] [DOI] |
| 56. | Neu B, Puschmann AJ, Mayerhofer A, Hutzler P, Grossmann J, Lippl F, Schepp W, Prinz C. TNF-αlpha induces apoptosis of parietal cells. Biochem Pharmacol. 2003;65:1755-1760. [PubMed] [DOI] |
| 57. | Sakumoto R, Shibaya M, Okuda K. Tumor necrosis factor-alpha (TNF alpha) inhibits progesterone and estradiol-17beta production from cultured granulosa cells: presence of TNFalpha receptors in bovine granulosa and theca cells. J Reprod Dev. 2003;49:441-449. [PubMed] [DOI] |
| 58. | Satici A, Guzey M, Dogan Z, Kilic A. Relationship between Tear TNF-αlpha, TGF-beta1, and EGF levels and severity of conjunctival cicatrization in patients with inactive trachoma. Ophthalmic Res. 2003;35:301-305. [PubMed] [DOI] |
| 59. | Azzolina A, Bongiovanni A, Lampiasi N. Substance P induces TNF-αlpha and IL-6 production through NF kappa B in peritoneal mast cells. Biochim Biophys Acta. 2003;1643:75-83. [PubMed] [DOI] |
| 60. | Fukamachi H, Fukuda K, Suzuki M, Furumoto T, Ichinose M, Shimizu S, Tsuchiya S, Horie S, Suzuki Y, Saito Y. Mesenchymal transcription factor Fkh6 is essential for the development and differentiation of parietal cells. Biochem Biophys Res Commun. 2001;280:1069-1076. [PubMed] [DOI] |
| 61. | Kaestner KH, Silberg DG, Traber PG, Schütz G. The mesenchymal winged helix transcription factor Fkh6 is required for the control of gastrointestinal proliferation and differentiation. Genes Dev. 1997;11:1583-1595. [PubMed] [DOI] |
| 62. | Kamimura H, Konda Y, Yokota H, Takenoshita S, Nagamachi Y, Kuwano H, Takeuchi T. Keχ2 family endoprotease furin is expressed specifically in pit-region parietal cells of the rat gastric mucosa. Am J Physiol. 1999;277:G183-G190. [PubMed] |
| 63. | Henrich S, Cameron A, Bourenkov GP, Kiefersauer R, Huber R, Lindberg I, Bode W, Than ME. The crystal structure of the proprotein processing proteinase furin explains its stringent specificity. Nat Struct Biol. 2003;10:520-526. [PubMed] [DOI] |
| 64. | Wu C, Wu F, Pan J, Morser J, Wu Q. Furin-mediated processing of Pro-C-type natriuretic peptide. J Biol Chem. 2003;278:25847-25852. [PubMed] [DOI] |
| 65. | Mayer G, Boileau G, Bendayan M. Furin interacts with proMT1-MMP and integrin alphaV at specialized domains of renal cell plasma membrane. J Cell Sci. 2003;116:1763-1773. [PubMed] [DOI] |
| 66. | Stewart LA, van Driel IR, Gleeson PA. Perturbation of gastric mucosa in mice expressing the temperature-sensitive mutant of SV40 large T antigen. Potential for establishment of an immortalised parietal cell line. Eur J Cell Biol. 2002;81:281-293. [PubMed] [DOI] |
| 67. | Franic TV, Judd LM, Robinson D, Barrett SP, Scarff KL, Gleeson PA, Samuelson LC, Van Driel IR. Regulation of gastric epithelial cell development revealed in H(+)/K(+)-ATPase beta-subunit- and gastrin-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2001;281:G1502-G1511. [PubMed] |
| 68. | Caruso RA, Fabiano V, Rigoli L, Inferrera A. Focal parietal cell differentiation in a well-differentiated (intestinal-type) early gastric cancer. Ultrastruct Pathol. 2000;24:417-422. [PubMed] [DOI] |
| 69. | Okabe S. Hypothesis--origin of parietal cells: transfer of the H+K+-ATPase gene from parasitic microorganisms to Cnidaria? Chin J Physiol. 1999;42:121-128. [PubMed] |
| 70. | Armando Sánchez J, Lasker HR, Taylor DJ. Phylogenetic analyses among octocorals (Cnidaria): mitochondrial and nuclear DNA sequences (lsu-rRNA, 16S and ssu-rRNA, 18S) support two convergent clades of branching gorgonians. Mol Phylogenet Evol. 2003;29:31-42. [PubMed] [DOI] |