STUDY OF THE MECHANISM OF PEPSINOGEN SECRETION.

为了探讨胃蛋白酶原分泌（PS）的机制，我们进行了三条线的研究，得到了以下结果。(1)观察了激动剂和细胞内信使对分离青蛙胃蛋白酶原腺泡蛋白的影响。肾上腺素能、胆碱能和bombesin刺激引起PS呈剂量相关性升高，后两者同时引起[Ca^<2+>]i升高。DBcAMP、TPA和A23187均可引起胃蛋白酶原分泌量的剂量相关增加，三者的任意组合均可引起PG的加性或增强性相互作用。cAMP, [Ca^<2+>]i和蛋白激酶C，以及[Ca^<2+>]i在脱敏的发展中起重要作用。(2)在离体青蛙氧合细胞中观察到K^+通道和地窖电位。最常见的观察到的通道的单位电导为30- 35ps，由DBcAMP和组胺激活。高电导的55 ~ 60ps通道被胆碱能刺激和Ca^<2+>离子载体激活。这些通道对K^+都有很高的选择性。电流的大小减小了Mg^<2+>。奥美拉唑抑制了两个K^+通道。这些结果表明，K^+通道受分泌物和细胞内信使的调节，并可能负责维持膜电位。(3)奥美拉唑在实验和临床观察中均能提高PS。奥美拉唑的作用可能不涉及膜受体的功能。

To investigate the mechanism of pepsinogen secretion (PS), the three lines of studies have been done, and the following results were obtained.(1) The effects of agonists and intracellular messengers on the PS was observed in isolated frog pepsinogen acini. Adrenergic, cholinergic and bombesin stimulation caused dose-related increase in PS, and the latter two of them caused the increase in [Ca^<2+>]i simultaneously. DBcAMP, TPA and A23187 caused dose-related increase in pepsinogen secretion, any combination of the secretagogues caused additive or potentiative interaction in PG. The results suggest that the mechanism of PS involves three messenger pathways; cAMP, [Ca^<2+>]i and protein kinase C, and that [Ca^<2+>]i play a important role in the development of desensitization.(2) K^+ channels and cellar electrical potential were observed in the isolated frog oxyntic cells. The most frequent observed channels had a unit conductance 30-35 pS which was activated by DBcAMP and histamine. The higher conductance 55-60 PS channel was activated by cholinergic stimulation and Ca^<2+> ionophore. These channels were both highly selective for K^+. The magnitude of currents was reduced by Mg^<2+>. The two K^+ channels were inhibited by omeprazole. These results indicate that the K^+ channels are regulated by the secretagogues and intracellar messengers, and may be responsible for maintenance of membrane potential.(3) Omeprazole increased PS in both experimental and clinical observation. The effect of omeprazole may be not involve in the function of membrane receptors.