REGULATION OF TRACHEAL SECRETORY CELLS: ROLE OF CAMP

本项目旨在研究在体内和体外循环的作用， AMP在调节离子、水、粘液、糖蛋白和 来自狗、猫和狗体内特定细胞类型的炎症介质， 雪貂气管 利用免疫细胞化学技术， 气道分泌细胞内cAMP的变化 神经、药理学或刺激剂的刺激， 这些细胞的生理反应。 我会把联合收割机， 免疫药理学和解剖学方法来研究： 犬、猫和雪貂气管中cAMP的亚细胞定位; 环磷酸腺苷水平之间的关系表明， 在特定细胞类型和环核苷酸内免疫细胞化学 在整个组织中化学测量的浓度;体液免疫的影响 与副交感神经和交感神经通路的神经刺激相比， 花生四烯酸代谢物和细菌毒素对环AMP水平的影响 通过免疫细胞化学和蛋白结合测定， 运输和分泌。 作为多学科研究的一部分， 心血管研究中肺和气道的神经体液调节 研究所，这个项目将集中在神经和体液机制 调节气管中的细胞功能。 我会用 免疫细胞化学和生物化学方法来评估循环的作用， 一磷酸腺苷启动和调节特定细胞分泌反应 检查这些细胞类型及其反应的形态学方法 刺激;以及生理学、药理学和生物化学方法 研究离子、糖蛋白和介质的运输和分泌 从这些细胞。 这些研究的结果将为以下方面提供见解： 调节气道对各种刺激的反应的机制。 的 环磷酸腺苷免疫细胞化学探针将提供以下信息 单个细胞的受体调节，这是无法从 环AMP的化学测定或这些细胞中受体的化学测量 组织中 这些信息将增加我们对疾病的理解， 如哮喘、慢性支气管炎和囊性纤维化， 在分泌中起主要作用。

This project is designed to examine in vivo and in vitro the role of cyclic AMP in modulating the secretion of ions, water, mucous, glycoproteins, and inflammatory mediators from specific cell types within the dog, cat, and ferret trachea. Using immunocytochemical techniques I will correlate changes in intracellular cyclic AMP in airway secretory cells in response to stimulation by neural, pharmacologic, or irritant agents with physiologic responses in these cells. I will combine physiologic, immunopharmacologic, and anatomic methods to study: the speciic cellular and subcellular localization of cyclic AMP in dog, cat, and ferret trachea; the relationship between cyclic AMP levels demonstrated immunocytochemically within specific cell types and cyclic nucleotide concentrations measured chemically in whole tissue; the effect of humoral versus neural stimulation of parasympathetic and sympathetic pathways, metabolites of arachidonic acid, and bacterial toxins on cyclic AMP levels measured immunocytochemically and by protein binding, and the relationship to transport and secretion. As part of the multidisciplinary study of neurohumoral regulation of lungs and airways at the Cardiovascular Research Institute, this project will focus on the nervous and humoral mechanisms which modulate cellular function in the trachea. I will use immunocytochemical and biochemical methods to evaluate the role of cyclic AMP in initiating and modulating secretory responses in specific cell types; morphologic methods to examine these cell types and their response to stimulation; and physiological, pharmacological, and biochemical methods to study the transport and secretion of ions, glycoproteins, and mediators from these cells. Results from these studies will provide insights into the mechanisms which mediate airway responses to a variety of stimuli. The immunocytochemical probe for cyclic AMP will provide information on receptor modulation of individual cells which is not available from chemical assays of cyclic AMP or chemical measurement of receptors in these tissues. This information will add to our understanding of diseases such as asthma, chronic bronchitis, and cystic fibrosis, in which abnormalities in secretion play a major role.