REGULATORY MECHANISMS IN GASTRIC ENZYME SECRETION

胃部分泌的胃蛋白酶原是胃蛋白酶的重要组成部分 消化过程。除了启动蛋白质消化，胃蛋白酶 释放作为刺激释放的多肽和氨基酸 调节荷尔蒙胃泌素和CCK。此外，胃蛋白酶在人体内的存在 胃液被认为增强了酸在形成胃液中的作用。 胃和十二指肠溃疡。这项研究计划的总体目标是 探讨胃蛋白酶原调节的生理机制 分泌物。拟议的研究将利用 以离体胃腺体为模型系统的体外研究 胃蛋白酶原分泌。这项建议有三个主要目的。 第一个目标是确定多肽荷尔蒙在刺激 胃蛋白酶原分泌。这些研究将集中在以下问题上： 胃泌素是胃蛋白酶原分泌的直接生理刺激。 人们普遍认为。放射性配基结合将用于表征 多肽受体并确定它们的细胞位置。此外, 将尝试确定在部分地区发现的一种肽刺激 纯化的十二指肠提取物。这些研究建议对原油进行分馏 高效液相色谱分离制备活性多肽及其组成鉴定 分析。该提案的第二个主要目的是试图理解 两种细胞内可分离物质存在的生理学意义 导致胃蛋白酶原分泌的机制。这个问题将是 用配基结合来确定细胞分布的探讨 与这两条通路相关的受体，并通过表征 这两种机制所引发的刺激模式。的最终目标是 该方案将采用一种新的渗透性胃液制剂 腺体研究细胞内对胃蛋白酶原的需求 放手。重点将放在研究离子的作用上 组成、pH和第二信使可能是调节的候选者 胃肠颗粒释放。

Secretion of pepsinogen by the stomach is an important component of the digestive process. In addition to initiating protein digestion, pepsins release peptides and amino acids which serve as stimuli for release of the regulatory hormones gastrin and CCK. Moreover, the presence of pepsins in gastric juice is believed to enhance the effect of acid in the formation of gastric and duodenal ulcers. The overall goal of this research program is to characterize the physiological mechanisms which regulate pepsinogen secretion. The proposed research will take advantage of the development of isolated gastric glands as a model system for the in vitro study of pepsinogen secretion. There are three major aims of the present proposal. The first aim is to identify the role of peptide hormones in stimulating pepsinogen secretion. These studies will focus on the question of whether gastrin is a direct physiological stimulus for pepsinogen secretion as is generally believed. Radioligand binding will be used to characterize peptide receptors and identify their cellular location. In addition, attempts will be made to identify a peptide stimulus found in partially purified duodenal extracts. These studies propose to fractionate the crude preparation using HPLC and identify active peptides through compositional analysis. The second major aim of the proposal seeks to understand the physiological significance of the existence of two separable intracellular mechanisms leading to pepsinogen secretion. This question will be approached using ligand binding to define the cellular distribution of receptors associated with the two pathways and by characterizing the pattern of stimulation elicited by the two mechanisms. The final aim of the proposal will employ a novel preparation of permeabilized gastric glands to investigate the intracellular requirements for pepsinogen release. Emphasis will be placed on examining the roles of ionic composition, pH and second messengers as possible candidates for regulating peptic granule release.