PHYSIOLOGY OF THE ISOLATED MAMMALIAN PARIETAL CELL

酸的分泌受到无数化学递质传递的调节。 通过血液、神经和局部组织储存进入眼底粘膜。 这个更新建议是基于假设这些路径 调节胃酸分泌在眼底的多个点上相互作用 粘膜，在最终的靶细胞和调节递送 内分泌/旁分泌递质。这项建议最广泛的目的是 进一步说明管理这些发射机交付的因素，并 受体的性质、位置和细胞调节机制 它们对顶叶细胞和生长抑素细胞的影响。方法是 用酶还原法从犬胃底粘膜分离细胞 治疗。细胞将通过速度和密度细胞技术进行分离 并使用各种免疫组织化学、内分泌和 生化标记物。胃泌素刺激顶叶的双重作用 细胞和引起生长抑素的释放，强调了 描述抑制通路和刺激通路之间的相互作用。 因此，研究将集中在刺激因素(胃泌素和乙酰胆碱)上。 和抑制因素[促甲状腺激素释放激素(TRH)，表皮 生长因子(EGF)和生长抑素]。放射性配基技术，偶联 通过放射自显影，将被用来定位粘膜细胞上的受体 这些发射器中的每一个。受体的特性将是生物学的 对这些递质的反应，主要研究壁细胞功能 (弱碱基积累)与细胞生长抑素的释放 术语文化。介导刺激和细胞因子的机制和细胞元件 这些化学传递体的抑制作用将被研究，重点是 钙、蛋白质和受体磷酸化的作用。这种方法 以及了解调控因素之间相互作用的可能性 开发的技术将极大地增强壁细胞的功能 用于分离和鉴定质膜受体。 这项建议的长期目标是了解关键控制 正常生理中酸分泌的机制及其与 酸性消化系统疾病的高分泌及其对机体免疫功能的影响 治疗性干预。

Acid secretion is regulated by a myriad of chemical transmitters delivered to the fundic mucosa by blood and nerves and from local tissue stores. This renewal proposal is based upon the hypothesis these pathways regulating acid secretion interact at multiple points within the fundic mucosa, both at final target cells and modulating delivery of endocrine/paracrine transmitters. The broadest aim of this proposal is to further delineate the factors regulating delivery of these transmitters and the nature and locus of the receptors and cellular mechanisms mediating their effects on both parietal and somatostatin cells. The approach is reductionistic, isolating cells from canine fundic muocsa by enzyme treatment. Cells will be separated by velocity and density cell techniques and identified using a variety of immunohistochemical, endcrine, and biochemical markers. The dual effects of gastrin, to stimulate parietal cells and to cause the release of somatostatin, underline the importance of delineating the interactions between inhibitory and stimulatory pathways. Studies will thus focus on stimulatory elements (gastrin and acetylcholine) and inhibitory elements [thyrotropin releasing hormone (TRH), epidermal growth factor (EGF), and somatostatin]. Radioligand techniques, coupled with autoradiography, will be used localize receptors on mucosal cells for each of these transmitters. Receptor characterization will biological responses to these transmitters, primarily studying parietal cell function (weak base accumulation) and release of somatostatin from cells in short term culture. Mechanisms and cellular elements mediating stimulation and inhibition by these chemical transmitters will be studied, focusing on the role of calcium and protein and receptor phosphorylation. This approach and the potential for understanding the interplay of factors regulating parietal cell function will be greatly enhanced by developing techniques for isolation and characterization of the plasma membrane receptors. The long range goal of this proposal is to understand critical control mechanisms for acid secretion in normal physiology and as they relate to acid hypersecretion in acid peptic disease and influence the response to therapeutic intervention.