CELL SECRETION AND MEMBRANE FORMATION IN THE PANCREAS

这项提议的长期目标是继续审查 根尖和基底外侧的功能和生化特性 大鼠胰腺腺泡细胞的胞浆结构域及其相互关系 极化的腺上皮细胞中的刺激-分泌耦合，以及 定义在生成和维护 胚胎胰腺和大鼠腺泡内的有组织上皮 细胞瘤。首先，我们计划分离和表征生物化学 成年大鼠腺泡细胞顶端和基底外侧的质膜结构域 为研制用于研究的单抗做准备 根尖/基底侧膜的生物发生。研究还计划进行 表征细胞的拓扑分布和生化性质 CCK受体作为一种特定的基底侧膜蛋白的例子 125I标记CCK-8受体放射自显影和亲和标记 探测器。其次，我们建议用生化和生物化学来表征 免疫化学技术，发育调节的特性 可能参与细胞-细胞和细胞底物的质膜蛋白 相互作用伴随着极化的、功能性的 大鼠胚胎胰腺上皮细胞与CCK的个体发育 感受器。最后，使用一种可移植的大鼠腺泡细胞瘤 细胞重组为极化上皮与沉积有关 在体内，当基膜与间充质衍生组织接触时，我们 计划在体外直接检测基底膜和它的作用 极化上皮细胞的建立和维持中的成分 结构和细胞生长的调节。这些研究应该进一步 我们对基膜介导的机制的理解 正常组织发生所需的上皮-间充质相互作用 架构在胰腺发育期间和未来可能有助于 理解这种相互作用的潜在像差可能不充分 肿瘤转化和发育异常。

The long -range goal of this proposal is to continue to examine the functional and biochemical properties of the apical and basolateral plasmlemmal domains of the rat pancreatic acinar cell as they relate to stimulus-secretion coupling in a polarized glandular epithelial cell, and to define the factors involved in generation and maintenance of an organized epithelium both in the embryonic pancreas and in a rat acinar cell tumor. First, we plan to isolate and characterize biochemically the apical and basolateral plasmalemmal domains of the adult rat acinar cell preparatory to raising monoclonal antibodies for use in studies of apical/basolateral membrane biogenesis. Studies are also planned to characterize the topologic distribution and biochemical properties of the CCK receptor as an example of a specific basolateral membrane protein using autoradiography and affinity labeling with 125 I-labeled CCK-8 receptor probes. Second, we propose to characterize, using biochemical and immunochemical techniques, the properties of developmentally regulated plasmalemmal proteins that may be involved in cell-cell and cell-substratum interaction that accompany establishment of a polarized, functional epithelium in the embryonic rat pancreas including ontogeny of CCK receptors. Finally, using a transplantable rat acinar cell tumor whose cells reorganize into polarized epithelia in association with deposition of basal lamina when in contact with mesenchymally-derived tissues in vivo, we plan to examine directly in vitro the role of basal lamina and its components in establishment and maintenance of polarized epithelial structures and in regulatin of cell growth. These studies should further our understanding of the mechanisms wherein basal lamina mediates epithelial-mesenchymal interactions required for genesis of normal tissue architecture during pancreatic development and in the future may help in understanding potential aberrations of this interaction that may underly neoplastic transformation and developmental abnormalities.