REGULATORY MECHANISMS IN GASTRIC ENZYME SECRETION

胃分泌胃蛋白酶原是胃肠道的重要组成部分。 消化过程 除了启动蛋白质消化外，胃蛋白酶 释放肽和氨基酸，其作为刺激物用于释放 调节激素胃泌素和CCK。 此外，胃蛋白酶的存在， 胃液被认为增强了酸在形成 胃和十二指肠溃疡。 这项研究计划的总体目标是 表征调节胃蛋白酶原的生理机制 分泌物 拟议的研究将利用发展 离体胃腺作为体外研究的模型系统， 胃蛋白酶原分泌 本提案有三个主要目标。 第一个目的是确定肽激素在刺激 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物， 一般相信。 放射性配体结合将用于表征 肽受体，并确定其细胞位置。 此外，本发明还提供了一种方法， 将尝试鉴定在部分细胞中发现的肽刺激物， 纯化的十二指肠提取物。 这些研究建议对原油进行压裂 使用HPLC制备并通过组成鉴定活性肽 分析. 该提案的第二个主要目的是了解 两个可分离的细胞内存在的生理意义 导致胃蛋白酶原分泌的机制。 该问题将被 使用配体结合来确定细胞分布的方法 受体与这两个途径，并通过表征 两种机制引起的刺激模式。 的最终目的 该提案将采用一种新透化胃粘膜制剂 研究胃蛋白酶原的细胞内需求 release. 重点将放在检查离子的作用 组成，pH值和第二信使作为可能的候选人， 消化颗粒释放。

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.