Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interactions between putative second effector mechanisms for hydrogen ion secretion were studied in isolated gastric cell preparations of the rat containing 60-70% parietal cells. Dibutyryl-cAMP and the compounds which increased the level of cAMP (histamine plus rolipram and forskolin plus rolipram) inhibited the carbachol-induced accumulation of [3H]inositol tris-, bis- and monophosphate. There was both a temporal and quantitative correlation between the increase in cAMP and the inhibition of the accumulation of [3H]inositol phosphates. Cimetidine attenuated the inhibitory effect of histamine on the formation of [3H]inositol phosphates. The enhancement of the accumulation of [3H]inositol phosphates by various concentrations of carbachol affected neither the basal nor the histamine-stimulated cAMP levels. In contrast to dibutyryl-cAMP, dibutyryl-cGMP did not modify the carbachol-induced formation of [3H]inositol phosphates. The biologically active phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), which activates protein kinase C, inhibited both the basal and carbachol-induced accumulation of [3H]inositol phosphates. We suggest that the inhibition of the formation of inositol trisphosphate by the increase in the intracellular level of cAMP and by the activation of protein kinase C might be intracellular negative feedback systems which prevent the overreaction of the acid-secreting parietal cells under the simultaneous influence of the physiological gastric secretagogues.
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PMID:Interactions between intracellular cyclic AMP and agonist-induced inositol phospholipid breakdown in isolated gastric mucosal cells of the rat. 283 May 43

The effect of histamine on the phosphoinositide turnover and intracellular free calcium activity [Ca2+]i was examined in human glomerular epithelial cells in culture. Addition of histamine to glomerular epithelial cells resulted in formation of inositol phosphates in a time- and dose-dependent manner. A transient maximum of inositol trisphosphate (InsP3) was observed within 10 s. Stimulation of protein kinase C by short-term pretreatment (15 min) of glomerular epithelial cells with phorbol 12-myristate 13-acetate caused a dose-dependent inhibition of the histamine-induced inositol phosphate accumulation. The baseline of [Ca2+]i in the cells was 115 +/- 2.7 nmol/l (n = 103). Histamine (ED50: approx. 2 x 10(-7) mol/l) caused a rapid and transient increase in [Ca2+]i as detected by fura-2 microfluorimetry studies. In a calcium-free extracellular solution the rapid increase of [Ca2+]i was still present. The H1 receptor antagonist mepyramine (IC50: approx. 8 x 10(-9) mol/l) inhibited the histamine (10(-6) mol/l) response on [Ca2+]i. Cimetidine, a potent H2 receptor antagonist, showed no effect. This data indicates that H1 receptor activation causes hydrolysis of phosphatidylinositol 4, 5-bisphosphate by phospholipase C activation, and consecutive mobilization of intracellular calcium. Since histamine is a mediator of inflammation, antigen response and cellular injury, these findings could be of importance for the understanding of glomerular epithelial cell pathology.
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PMID:Effects of histamine on inositol phosphates and intracellular Ca2+ in human glomerular epithelial cells. 797 Jan 17

Neutrophil-endothelial adhesion is a crucial step in vascular inflammation and is recognized as a direct cause of serious atherosclerosis-mediated diseases. We previously demonstrated that high concentrations of glucose increased adhesion in a protein kinase C (PKC)-dependent manner within 48 h of administration by increasing the surface expression of endothelial adhesion molecules. In this study, we focused on the effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion and on the surface expression of endothelial adhesion molecules mediated by high glucose levels. Histamine 2 receptor antagonists have pleiotropic effects; they not only block the secretion of gastric acid, but also inhibit cell-cell adhesion, resulting in inhibition of metastasis. However, relevant mechanisms of action are not yet fully understood. Of three histamine 2 receptor antagonists (cimetidine, ranitidine, and famotidine), only cimetidine significantly attenuated adhesion mediated by 48-h incubation with 27.8 mM glucose. Cimetidine was found to decrease the surface expression of endothelial adhesion molecules intercellular adhesion molecule-1 and P-selectin, but not E-selectin. To determine the effects of cimetidine on intracellular level, we examined the effects of cimetidine on PKC-induced changes in adhesion, as well as the effects of nitric oxide (NO) synthase inhibitors on cimetidine. We found that NO synthase inhibitors reduced the inhibitory effects of cimetidine, whereas cimetidine did not affect adhesion mediated by a PKC activator. These data suggest that cimetidine acts directly on endothelial cells to inhibit high-glucose-induced expression of adhesion molecules and neutrophil adhesion mediated by increasing endothelial NO production, but not by inhibiting PKC.
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PMID:Effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion and surface expression of endothelial adhesion molecules induced by high glucose levels. 1718 74