STUDY OF THE MECHANISM OF PEPSINOGEN SECRETION.

胃蛋白酶原分泌机制的研究。

• 批准号: 62480196
• 负责人: INOUE Masaki
• 金额: $ 1.6万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480196/
• 关键词: pepsinogen secretion; calcium ion; cAMP; potacium channel; membrane potential; omeprazole; パッチクランプ法; Pepsinogen分泌; 細胞内free Ca^<2+>; cAMP; diacylglycerol; K^+-channel; ペプシノーゲン分泌; ベサネコール; ボンベシン; ジブチリルcAMP

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.

为了研究胃蛋白原分泌（PS）的机制，已经完成了三种研究，并获得了以下结果。（1）在分离的青蛙胃蛋白原acini中观察到激动剂和细胞内信使对PS的影响。肾上腺素能，胆碱能和bombesin刺激导致PS的剂量相关，后两个同时导致[Ca^<2+>] I的增加。 DBCAMP，TPA和A23187导致胃蛋白原分泌与剂量相关的增加，促分子的任何组合在PG中引起添加剂或增强性相互作用。结果表明，PS的机制涉及三个使者途径。 CAMP，[Ca^<2+>] I和蛋白激酶C，并且[Ca^<2+>] I在脱敏的发展中起重要作用。（2）在分离的青蛙氧细胞中观察到K^+通道和地窖电势。最频繁的观察到的通道的单位电导率为30-35 PS，该通道被DBCAMP和组胺激活。通过胆碱能刺激和CA^<2+>离子载体激活较高的电导55-60 PS通道。这些通道对K^+都是高度选择性的。 Mg^<2+>降低了电流的大小。奥美拉唑抑制了两个K^+通道。这些结果表明，K^+通道受到促分子和内部内使者的调节，并可能负责维持膜电位。（3）奥美拉唑在实验和临床观察中都增加了PS。奥美拉唑的作用可能不参与膜受体的功能。

项目成果

白川敏夫,井上正規,梶山梧朗他: "Omeprazoleの酸、並びにペプシノ-ゲン分泌に及ぼす影響に関する検討" 胃分泌研究会誌. 20. 117-120 (1988)

Toshio Shirakawa、Masanori Inoue、Goro Kajiyama 等人：“奥美拉唑对胃酸和胃蛋白酶原分泌的影响的研究”胃分泌研究学会杂志 20. 117-120 (1988)。

井上正規: "ペプシノ-ゲン分泌に関する実験的研究ーbiologically active peptideの影響についてー" 第30回ペプシン研究会記念シンポジウム「ペプシン・抗ペプシン剤の臨床」. 123-136 (1988)

Masanori Inoue：“胃蛋白酶原分泌的实验研究-生物活性肽的影响”第30届胃蛋白酶研究组纪念研讨会“胃蛋白酶和抗胃蛋白酶制剂的临床应用”123-136（1988）。

T.Shirakawa;B.I.Hirschowitz: Am.J.Physiol.250. 484-488 (1986)

T.Shirakawa；B.I.Hirschowitz：Am.J.Physiol.250。

T.Shirakawa;B.I.Hirschowitz: Am.J.Physiol.250. 668-673 (1986)

T.Shirakawa；B.I.Hirschowitz：Am.J.Physiol.250。

井上正規: 日本消化器病学会雑誌. 83. 608-618 (1986)

Masanori Inoue：日本胃肠病学会杂志 83. 608-618 (1986)