MECHANISMS OF PEPSINOGEN SECRETION FROM CHIEF CELLS

对细胞机制的了解相对较少。 主细胞分泌胃蛋白酶原。一个主要的障碍是缺乏 其主要细胞含量均一的制剂和 对刺激有反应的。最近，首席调查员 豚鼠分散主细胞制备方法的改进 对促分泌剂有反应的胃。主细胞占90% 最终的细胞悬浮液和5倍的胃蛋白酶原分泌刺激 观察到促分泌剂的作用可能是通过 环状AMP(促胰液素)或钙(氨基甲酰胆碱、缩胆囊素)。在……里面 我们提出的目前的研究计划是利用这种准备来测量 不同促分泌剂对细胞内钙和循环的直接影响 安培。细胞内钙离子通量的测定将通过负载分散的钙离子来实现 含45Ca的细胞，与促分泌剂孵育，并测量细胞 放射性。细胞环磷酸腺苷将通过孵育来测量 含促分泌剂的分散主细胞与细胞环磷酸腺苷的测定 通过放射免疫分析。为了建立这些细胞之间的关系 事件和酶的分泌，细胞将在条件下孵化 与上述类似，将测量胃蛋白酶原分泌量。通过 分散的主细胞分泌酶的变化与变化的关系 在细胞钙和环状AMP中，将有可能建立 这些细胞介质在胃蛋白酶原分泌中的作用。 如果成功，这些研究将阐明 胃蛋白酶原分泌。此外，通过检查组合的效果， 促分泌剂对胃蛋白酶原分泌的影响及其与细胞变化的关系 钙和环磷酸腺苷也有可能确定细胞 加强促分泌剂之间相互作用的基础。这些研究 与消化性溃疡疾病的发病机制有关 可能会提出抑制胃蛋白酶原分泌的方法。 无序。此外，由于已经注意到 主细胞的胃蛋白酶原分泌和其他细胞的酶分泌 组织，这些研究将对理解细胞 在各种组织中调节酶的分泌。

Relatively little is known about the cellular mechanisms involved in pepsinogen secretion from chief cells. A major obstacle has been the lack of a preparation that is homogeneous in its chief cell content and responsive to stimulation. Recently, the principal investigator has developed methods for preparing dispersed chief cells from guinea pig stomach that are responsive to secretagogues. Chief cells constitute 90% of the final cell suspension and 5-fold stimulation of pepsinogen secretion is observed with secretagogues whose actions are probably mediated by cyclic AMP (secretin) or calcium (carbamylcholine, cholecystokinin). In the present research plan we proposed to use this preparation to measure directly the effect of various secretagogues on cellular calcium and cyclic AMP. Cellular calcium fluxes will be measured by loading dispersed chief cells with 45Ca, incubating with secretagogues, and measuring cellular radioactivity. Cellular cyclic AMP will be measured by incubating dispersed chief cells with secretagogues and measuring cellular cyclic AMP by radioimmunoassay. To establish the relation between these cellular events and enzyme secretion, cells will be incubated under conditions similar to those above and pepsinogen secretion will be measured. By relating changes in enzyme secretion from dispersed chief cells to changes in cellular calcium and cyclic AMP, it will be possible to establish the role of these cellular mediators in pepsinogen secretion. If successful, these studies will elucidate the cellular mechanisms of pepsinogen secretion. Moreover, by examining the effect of combinations of secretagogues on pepsinogen secretion in relation to changes in cellular calcium and cyclic AMP it may also be possible to determine the cellular basis for potentiating interactions between secretagogues. These studies have implications regarding the mechanisms of peptic ulcer disease and might suggest methods for inhibiting pepsinogen secretion in this disorder. Furthermore, because similarities have been noted between pepsinogen secretion from chief cells and enzyme secretion from other tissues, these studies will be important for understanding cellular mediation of enzyme secretion in a variety of tissues.