CELL SECRETION AND MEMBRANE FORMATION IN THE PANCREAS

这项建议的长远目标是继续研究 顶侧和底侧的功能和生化特性 大鼠胰腺腺泡细胞的质膜结构域，因为它们与 极化腺上皮细胞中的刺激-分泌偶联，和 定义产生和维持一个 在胚胎胰腺和大鼠腺泡中的组织化上皮 细胞瘤 首先，我们计划分离和生物化学特性， 成年大鼠腺泡细胞的顶端和基底外侧质膜区 制备单克隆抗体用于研究 顶/基底外侧膜生物发生。 研究还计划 描述了拓扑分布和生化性质的 CCK受体作为特异性基底外侧膜蛋白的实例，使用 放射自显影和~（125）I-CCK-8受体亲和标记 probes. 其次，我们建议使用生物化学和 免疫化学技术，发育调节的性质， 质膜蛋白质可能参与细胞-细胞和细胞-基质 随着建立一个两极化、功能性 胚胎大鼠胰腺上皮细胞的研究 受体。 最后，使用可移植的大鼠腺泡细胞肿瘤， 细胞重组成极化的上皮细胞， 当在体内与间充质来源的组织接触时，我们 计划在体外直接检查基膜及其 极化上皮细胞的建立和维持 结构和调节细胞生长。 这些研究应进一步 我们对基底膜介导的机制的理解 正常组织发生所需的上皮-间质相互作用 在胰腺发育过程中的结构，并在未来可能有助于 了解这种相互作用的潜在畸变， 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.