Functional characterization and expression of PBR in rat gastric mucosa: stimulation of chloride secretion by PBR ligands.
Functional characterization and expression of PBR in rat gastric mucosa: stimulation of chloride secretion by PBR ligands.
复制标题
大鼠胃粘膜 PBR 的功能特征和表达：PBR 配体刺激氯离子分泌。
DOI：
10.1152/ajpgi.00290.2003
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Lacapere,J-J
中科院分区：
文献类型：
--
作者：
Ostuni,MA;Marazova,K;Peranzi,G;Vidic,B;Papadopoulos,V;Ducroc,R;Lacapere,J-J
以前的研究表明，胃粘膜中含有高水平的多肽安定结合抑制物，这是外周型苯二氮卓类受体(PBR)的内源性配体。然而，该受体蛋白在这些组织中的表达和功能尚未被研究。免疫组织化学显示，PBR免疫反应在大鼠胃底粘液细胞、壁细胞和胃窦粘液细胞中呈强阳性。免疫电子显微镜显示PBR在这些细胞内的线粒体定位。异喹啉PK 11195和苯二氮卓类药物Ro5-4864与胃膜的结合表明，胃底比胃窦有更多的PBR结合部位，对PK 11195的亲和力比Ro5-4864高。在Ussing小室中，在GABA和中枢性苯二氮卓类受体阻断剂存在下，PK 11195和Ro5-4864以浓度依赖的方式增加胃底和胃窦粘膜的短路电流。这种升高在外源性Cl-−替代后被消除，并且对氯离子通道或转运蛋白抑制剂敏感。PK 11195诱导的氯离子分泌对维拉帕米和细胞外钙耗竭敏感，可被塔普西林和细胞内钙耗竭所阻断，可被线粒体孔转换复合体抑制剂环孢菌素A阻断。PK 11195对H+的分泌没有直接影响，表明它刺激胃底粘膜不依赖酸分泌的Cl−的分泌。这些结果表明，胃粘膜的粘液细胞和壁细胞表达线粒体PbR，功能上偶联于钙依赖的Cl-−的分泌，可能参与胃粘膜的保护作用。
Previous studies have demonstrated that gastric mucosa contained high levels of the polypeptide diazepam binding inhibitor, the endogenous ligand of the peripheral-type benzodiazepine receptor (PBR). However, the expression and function of this receptor protein in these tissues have not been investigated. Immunohistochemistry identified an intense PBR immunoreactivity in the mucous and parietal cells of rat gastric fundus and in the mucous cells of antrum. Immunoelectron microscopy revealed the mitochondrial localization of PBR in these cells. Binding of isoquinoline PK 11195 and benzodiazepine Ro5–4864 to gastric membranes showed that fundus had more PBR-binding sites than antrum, displaying higher affinity for PK 11195 than Ro5–4864. In a Ussing chamber, PK 11195 and Ro5–4864 increased short-circuit current (Isc) in fundic and antral mucosa in a concentration-dependent manner in the presence of GABAAand central benzodiazepine receptor (CBR) blockers. This increase inIscwas abolished after external Cl−substitution and was sensitive to chloride channels or transporter inhibitors. PK 11195-induced chloride secretion was also1) sensitive to verapamil and extracellular calcium depletion,2) blocked by thapsigargin and intracellular calcium depletion, and3) abolished by the mitochondrial pore transition complex inhibitor cyclosporine A. PK 11195 had no direct effect on H+secretion, indicating that it stimulates a component of Cl−secretion independent of acid secretion in fundic mucosa. These data demonstrate that mucous and parietal cells of the gastric mucosa express mitochondrial PBR functionally coupled to Ca2+-dependent Cl−secretion, possibly involved in the gastric mucosa protection.