ONTOGENY OF GASTRIC HCL SECRETION

胃 HCL 分泌的个体发育

• 批准号: 3238594
• 负责人: JOHN G FORTE
• 金额: $ 11.54万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3238594
• 关键词: adenosinetriphosphatase; apical membrane; cell differentiation; cell membrane; cytoplasm; growth /development; hydrochloric acid; membrane activity; membrane reconstitution /synthesis; messenger RNA; secretion; stomach

Secretion of HCl by the gastric oxyntic cell is a highly specialized process involving coordinated 1) secretagogue-receptor interaction, 2) cytoplasmic activation, 3) recruitment of cytoplasmic membranes into the apical cell surface, and 4) operation of highly energetic transport pathways. The developing system offers a unique opportunity to study the molecular features and limitations in the series of events that underlie HCl secretion. Morphological differentiation of the oxyntic cell occurs rather rapidly, indicating defined periods of high synthesis for particular elements of the secretory apparatus. We propose to evaluate the ontogeny of individual components of the secretory apparatus along with the ultrasturctural development of the oxyntic cell and the ability to transport HCl. The development of the H+ pump enzyme, H,K-ATPase, will be studied and correlated with the pattern of tubulovesicle synthesis within the cell. Specific enzyme activity, total enzyme quantity and relative rates of synthesis of the pump enzyme will be determined. H+ transport activity of isolated membrane fractins deriving from cytoplasmic tubulovesicles will be studied and compared with H+, K+ and C1- transport with membranes that have been transformed (by fusion) into the apical cell surface. The ontogeny of oxyntic cell secretagogue-receptor activity will be established and compared with the appearance of intracellular second messenger activating systems as well as the capacity of the various transport pathways. Pathways for membrane synthesis during cytodifferentiation and membrane flow during the secretory cycle will be established. Analysis of mRNA durig oxyntic cell differentiation will seek to identify stages where specifically coded messages, such as that for H,K-ATPase synthesis, are in high abundance. These studies will provide a comprehensive picture of the chronology for expression of surface receptors. intracellular activators, transport enxymes, and ion channels that constitute the integrated secretory machinery of the oxyntic cell. The ontogenic appearance of specific proteins and transport pathways will also serve as identifying markers and help to establish their relative importance in the process of HCl secretion.

胃泌酸细胞分泌盐酸是一种高度专业化的 涉及协调的过程1）促分泌素-受体 相互作用，2）细胞质激活，3）募集 细胞质膜进入顶端细胞表面，和4） 高能量运输途径的运作。 发展中 系统提供了一个独特的机会来研究分子 HCl事件的特点和局限性 分泌物 泌酸细胞的形态分化 发生得相当快，表明高合成的确定时期 分泌器官的特殊成分。 我们建议 评估分泌的单个组分的个体发育 器官沿着超微结构的发展， 泌酸细胞和运输HCl的能力。 的发展 H+泵酶，H，K-ATP酶，将被研究和关联 与细胞内管状囊泡合成的模式相吻合。 比酶活、总酶量和相对酶活 测定泵酶的合成速率。 H+ 分离膜组分的转运活性， 将研究细胞质小管囊泡并与H+进行比较， K+和C1-与已转化的膜的转运 (by融合）进入顶端细胞表面。 泌酸的个体发生 将建立细胞促分泌素-受体活性， 与细胞内第二信使的出现相比， 激活系统以及各种运输的能力 途径。 膜合成途径 分泌周期中的细胞分化和膜流动 将建立。 胃泌酸细胞mRNA的分析 差异化将寻求确定阶段， 编码的信息，如用于H，K-ATP酶合成的信息， 高丰度。 这些研究将提供全面的 表面受体表达的时间顺序图。 细胞内激活剂、转运酶和离子通道， 构成泌酸细胞的整合分泌机制。 特异性蛋白质的个体发育外观和转运 路径也将作为识别标记，并帮助 确定它们在HCl工艺中的相对重要性 分泌物