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

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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