Studies on the gastro-duodenal diseases caused by signal transductlon abnormality in parietal cells

壁细胞信号转导异常引起的胃十二指肠疾病的研究

• 批准号: 07670615
• 负责人: TANI Norio
• 金额: $ 1.41万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670615/
• 关键词: parietal cell; acid secretion mechanism; signal transduction; sigma receptor; Platelet Activating Factor; local anesthetics; vacuolating toxin; protein kinase C; oxethazaine; procaine; 受容体; second messenger; PAF受容体; procain

Following research results were obtained using isolated parietal cells of guinea pig.1) Experimental studies using di-ortho-tolyl guanidine, a sigma receptor antagonist, demonstrated that sigma receptors may exist on parietal cells and that they may play a role in acid production via an increase in intracellular Ca^<++> concentration.2) It was demonstrated that PAF (platelet activating factor) which is known to be one of the factors relevant to pathogenesis of peptic ulcer may have receptors on parietal cells and that it may play a role in acid secretion via an increase in intracellular Ca^<++> concentration.3) Vacuolating toxin which is produced by Helicobacter pylori, a gram-negative bactelium infecting in human gastric epithelium, showed direct inhibitory action on the parietal cells. It is speculated that this toxin may act on H^+/K^+ ATPase because it induced no change in intracellular concentration of both cyclic AMP and Ca^<++> and because it inhibited not only histamine-induced … More acid secretion but also carbachol-or gastrin-induced acd secretion.4) The direct effects of procaine and oxethazaine on parietal cells were investigated because several reports have shown that local anesthetics have high affinity for muscarinic receptors and competitively inhibit the effects induced by cholinergic agents in various tissues. Procaine appears to display roughly similar action to carbachol through muscarinic receptors, while oxethazaine displays inhibitory action mainly by mechanisms other than inhibition at the muscarinic receptor site.5) It was revealed by Nothern blot analysis that alpha-and gamma-PKC (protein kinase C) isoforms were expressed in parietal cells. Both carbachol and gastrin incresed the level of alpha-and gamma-PKC mRNAs, but synthesis of zeta-PKC mRNA was not affected by these agonists. Histamine had no significant effect on the expression of alpha-, gamma-and zeta-PKC mRNAs. So alpha-and gamma-PKC isoforms may be involved in the regulation of gastric acid secretion. Less

使用分离的豚鼠壁细胞进行的研究结果如下：1)使用Sigma受体拮抗剂二邻甲苯基胍的实验研究表明，壁细胞上可能存在Sigma受体，它们可能通过增加细胞内钙离子浓度而在产酸中发挥作用。2)已知与消化性溃疡发病相关的因素之一--PAF(血小板激活因子)可能在壁细胞上有受体，并可能通过增加细胞内钙离子++&GT作用于酸分泌；3)幽门螺杆菌产生的空泡毒素对人胃上皮细胞有直接抑制作用。推测该毒素可能作用于H^+/K^+-…酶，因为它没有引起细胞内cAMP和钙离子浓度的变化，而且它不仅抑制组胺诱导的ATPase。更多的酸分泌，但卡巴胆碱或胃泌素诱导的ACD分泌。4)研究了普鲁卡因和奥沙扎因对壁细胞的直接作用，因为一些报道表明，局麻药对M受体具有高亲和力，并在各种组织中竞争性地抑制胆碱能药物的作用。普鲁卡因通过M受体表现出与卡巴胆碱大致相似的作用，而奥沙扎因则主要通过抑制M受体位置以外的机制发挥抑制作用。5)Northern印迹分析表明，α-和γ-PKC亚型在壁细胞中表达。卡巴胆碱和胃泌素均能增加α-和γ-PKC mRNAs水平，但对Zeta-PKC mRNAs的合成无影响。组胺对α-、γ-和Zeta-PKC mRNAs的表达无明显影响。因此，α-和γ-PKC亚型可能参与胃酸分泌的调节。较少

项目成果

宮沢 正行 ほか: "モルモット単離壁細胞を用いた,PAFの酸分泌に及ぼす影響の検討。" 消化管ホルモン. 13. 250-253 (1995)

Masayuki Miyazawa 等人：“使用豚鼠分离的壁细胞检查 PAF 对酸分泌的影响。”胃肠激素。

Suzuki T,et al.: "Changes in cytosolic free Ca^<++> by sigma receptor agonist in isolated guinea-pig parietal cells." Gut Hormones (Japanese Journal). 14. 33-35 (1996)

Suzuki T 等人：“在分离的豚鼠壁细胞中，σ 受体激动剂对胞质游离 Ca^< > 的变化。”

鈴木 孝良 ほか: "モルモット単離壁細胞の酸分泌機構におけるσ受容体の関与についての検討。" 消化管ホルモン. 13. 29-33 (1995)

Takayoshi Suzuki 等人：“关于 σ 受体参与离体豚鼠壁细胞酸分泌机制的研究。” 胃肠激素。 13. 29-33 (1995)

Suzuki T,et al.: "Studies on sigma receptor in gastric acid secretion using isolated guinea-pigparietal cells." Gut Hormones(Japanese Journal). 13. 29-33 (1995)

Suzuki T 等人：“使用分离的豚鼠顶细胞对胃酸分泌中的 sigma 受体进行研究。”

Tani N, et al.: "Effect of procaine and oxethazaine on muscarinic receptors of parietal cells." Tokai J.Exp.Clin.Med.22. (1997)

Tani N 等人：“普鲁卡因和奥沙嗪对壁细胞毒蕈碱受体的影响。”