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

利用分离的豚鼠顶骨细胞获得了以下研究结果。1)利用sigma受体拮抗剂-二邻基甲苯胍进行的实验研究表明，sigma受体可能存在于壁细胞上，并可能通过增加细胞内Ca^<++>浓度在产酸中发挥作用。2)发现血小板活化因子（血小板活化因子）作为消化性溃疡发病的相关因子之一，可能在壁细胞上有受体，并可能通过细胞内Ca^<++>浓度的升高而参与胃酸分泌。3)感染人胃上皮的革兰氏阴性杆菌幽门螺杆菌产生的空泡毒素对胃壁细胞有直接抑制作用。推测该毒素可能作用于H^+/K^+ atp酶，因为它没有引起细胞内环AMP和Ca^<++>浓度的变化，而且它不仅抑制组胺诱导的酸分泌，而且还抑制碳水化合物或胃泌素诱导的酸分泌。4)普鲁卡因和奥西嗪对壁细胞的直接作用被研究，因为一些报道表明局麻药对毒蕈碱受体具有高亲和力，并在多种组织中竞争性地抑制胆碱能药物诱导的作用。普鲁卡因似乎通过毒蕈碱受体表现出与恰巴醇大致相似的作用，而奥西嗪主要通过抑制毒蕈碱受体位点以外的机制表现出抑制作用。5) northern blot分析显示，α - pkc和γ - pkc（蛋白激酶C）亚型在壁细胞中表达。甲胆碱和胃泌素都增加了α - pkc mRNA和γ - pkc mRNA的水平，但这些激动剂不影响ζ - pkc mRNA的合成。组胺对α -、γ -和ζ - pkc mrna的表达无显著影响。因此- pkc和- pkc亚型可能参与胃酸分泌的调节。少

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