Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine secretion in rat peritoneal mast cells stimulated by nerve growth factor requires a synergistic signal delivered by lysophosphatidylserine. To study the signal-transducing system activated by these compounds, phospholipid metabolism has been investigated in these cells. Phospholipid labeling with 32PO4 reveals a 5-9-fold stimulation of phosphatidic acid, phosphatidylinositol and phosphatidylcholine synthesis. Increased synthesis of phosphatidylinositol is also monitored using [3H]inositol incorporation. When [3H]inositol-labeled mast cells are incubated in the presence of Li+, nerve growth factor and lysophosphatidylserine enhance the accumulation of inositol monophosphate, inositol bisphosphate and inositol trisphosphate. Similar to the induced histamine release, accumulation of inositol phosphates (a) does not occur when the two agonists are added separately; (b) is inhibited when lysophosphatidyl-L-serine is replaced by lysophosphatidyl-D-serine; and (c) is enhanced in the presence of extracellular Ca2+. The data suggest that the interactive stimulus of nerve growth factor and lysophosphatidylserine is transmitted through the polyphosphoinositide-phospholipase C system.
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PMID:Activation of phosphoinositide hydrolysis by nerve growth factor and lysophosphatidylserine in rat peritoneal mast cells. 245 74

To examine the role of protein kinase C (PKC) on the acid secretory activity of isolated rat parietal cells, histamine-and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-stimulated [14C]aminopyrine accumulation was determined in the presence of agents that redistribute PKC activity to plasma membranes. Phorbol 12-myristate 13-acetate (PMA), 1-oleoyl-2-acetylglycerol (OAG), and phospholipase C inhibited, in a dose-dependent fashion, histamine- and DBcAMP-stimulated [14C]aminopyrine accumulation. Because PKC inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) reversed the effect, the results suggest that inhibition of histamine- or DBcAMP-stimulated [14C]aminopyrine accumulation induced by PMA, OAG, or phospholipase C was caused by increased activity of PKC in plasma membrane. To determine where in the cascade of events PKC inhibits acid secretion, histamine-, cholera toxin-, and forskolin-stimulated [14C]aminopyrine accumulation was measured with or without PMA. Because the percent of inhibition by PMA of [14C]aminopyrine accumulation was similar with the three secretagogues, the results suggest that PKC inhibits acid secretion at a point beyond adenosine 3',5'-cyclic monophosphate (cAMP) production. This was supported by the fact that PMA had no effect on histamine-stimulated production of cAMP and by the finding that activation of PKC had the same effect on histamine- or DBcAMP-stimulated [14C]aminopyrine accumulation. Histamine and DBcAMP inhibited PKC activity, suggesting a reciprocal interaction between PKC and histamine-triggered signal transduction pathway.
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PMID:Interaction of signal transduction pathways in mediating acid secretion by rat parietal cells. 246 89

The ability of a variety of agonists to induce formation of inositol phosphates and 1,2-diacylglycerol in cultured adult human keratinocytes has been investigated. Histamine, bradykinin, and thrombin significantly stimulated formation of inositol mono-, bis-, and trisphosphate and 1,2-diacylglycerol within 5 min after addition. Aluminum fluoride also caused a dose-dependent accumulation of inositol phosphates suggesting the participation of a GTP binding protein in the regulation of phospholipase C-catalyzed phosphoinositide hydrolysis. These data demonstrate that human keratinocytes possess the capacity for phospholipase C-mediated signal transduction and suggest that this pathway may participate in the regulation of keratinocyte function.
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PMID:Agonist-induced hydrolysis of phosphoinositides and formation of 1,2-diacylglycerol in adult human keratinocytes. 247 31

Histamine increases microvascular permeability through a calcium-dependent process, and histamine occupancy of the H1-receptor increases calcium in cultured endothelial cells. Agents that increase adenosine 3',5'-cyclic monophosphate (cAMP) in endothelial cells prevent the in vivo increase in microvascular permeability that follows histamine exposure. In the current experiments, histamine occupancy of the H1-receptor increased the flux of albumin across monolayers of cultured human umbilical vein endothelial cells (HUVEC). This was prevented by pretreating the cells with theophylline, forskolin, and 8-bromo-cAMP (BrcAMP), which also decreased the flux of albumin across control monolayers. Exposing the cells to histamine increased inositol phosphate accumulation in the cells, and this was prevented by the H1-antagonist pyrilamine but not by theophylline, forskolin, and BrcAMP. Exposing the cells to histamine increased intracellular calcium measured with fura-2. The increase in cell calcium was prevented by pyrilamine but not by pretreatment with theophylline, forskolin, and BrcAMP. When endogenous cell GTP was depleted by permeabilizing the membranes of the endothelial cells with Staphylococcus aureus alpha-toxin, histamine-stimulated inositol phosphate accumulation was enhanced with addition of GTP but not with addition of GDP to the buffer. Addition of GTP alone to the buffer did not increase inositol phosphate accumulation in alpha-toxin-treated cells. Histamine stimulates inositol phosphate accumulation in HUVEC via a G protein. Inhibition of the edemagenic effects of histamine by cAMP does not occur by interrupting this signal transduction pathway between the binding of histamine to its receptor and the increase in intracellular calcium.
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PMID:Histamine and inositol phosphate accumulation in endothelium: cAMP and a G protein. 255 29

In order to analyze the complex activities of histamine H2 receptor activation on neutrophils, human HL-60 promyelocytic leukemia cells were differentiated into neutrophils by incubation with dimethyl sufoxide, loaded with the Ca2+-sensitive indicator dyes, indo-1 or fura-2, and the levels of intracellular Ca2+ ([Ca2+]i) measured in a fluorescent-activated cell sorter and fluorimeter, respectively. Histamine increased [Ca2+]i in a dose-dependent manner with a half-maximal concentration (EC50) of approximately 10(-6) to 10(-5) M, which exhibited H2 receptor specificity. Prostaglandin E2 and isoproterenol also induced [Ca2+]i mobilization in HL-60 cells, whereas the cell permeable form of cAMP and forskolin failed to increase [Ca2+]i. Since H2-receptor mediated [Ca2+]i mobilization was not inhibited by reducing the concentration of extracellular Ca2+ nor by the addition of Ca2+ channel antagonists, LaCl3 and nifedipine, [Ca2+]i mobilization is due to the release of Ca2+ from intracellular stores. Furthermore, both 10(-4) M histamine and 10(-6) M fMet-Leu-Phe increased the levels of 1,4,5-inositol trisphosphate. However, histamine-induced mobilization of [Ca2+]i was inhibited by cholera toxin but not by pertussis toxin, whereas the action of fMet-Leu-Phe was inhibited by pertussis toxin but not by cholera toxin. These data suggest that H2 receptors on HL-60 cells are coupled to two different cholera toxin-sensitive G-proteins and activate adenylate cyclase and phospholipase C simultaneously.
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PMID:Multiple signaling pathways of histamine H2 receptors. Identification of an H2 receptor-dependent Ca2+ mobilization pathway in human HL-60 promyelocytic leukemia cells. 255 5

The present study was undertaken to determine whether the phosphoinositide hydrolysis is responsible for the positive inotropic effect of histamine in guinea-pig left atria. Histamine induced hydrolysis of phosphoinositides and a positive inotropic effect in a concentration-dependent manner. These effects were antagonized by chlorpheniramine (0.1 mumol/l) but not by cimetidine (10 mumol/l). At a concentration of 1 mumol/l histamine produced a dual-component positive inotropic response composed of an initial increasing phase and a second and late developing, greater positive inotropic phase. Histamine (10 mumol/l) caused a gradual increase in the formation of [3H]inositol trisphosphate (IP3) and a significant increase in the [3H]IP3 level was detected 10 min after the stimulation. Thus, the increase in IP3 did not precede the increase in force of contraction. The phospholipase C inhibitors 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (100 mumol/l) and neomycin (100 mumol/l) significantly reduced the histamine-induced [3H]inositol monophosphate accumulation. However, pretreatment with the phospholipase C inhibitors did not affect the positive inotropic effect of histamine, either in its extent or in its pattern. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (100 nmol/l) and phorbol-12,13-dibutyrate (PDBu) (100 nmol/l) also significantly inhibited the phosphoinositide hydrolysis induced by histamine. The inhibitory effect of the phorbol esters on the phosphoinositide response was completely abolished in the presence of 10 mumol/l 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), a protein kinase C inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dissociation of phosphoinositide hydrolysis and positive inotropic effect of histamine mediated by H1-receptors in guinea-pig left atria. 255 50

Phosphoinositide hydrolysis does not appear to desensitize in 1321N1 astrocytoma cells. The evidence for this is that 1) the rate of accumulation of [3H]inositol 1-phosphate is linear for up to 90 min in the presence of carbachol, 2) pretreatment of cells with 100 microM carbachol for 75 min does not diminish the subsequent ability of carbachol to increase [3H]inositol 1-phosphate accumulation, and 3) the production of all of the [3H]inositol phosphates including the polyphosphoinositide metabolites [3H]inositol bis- and trisphosphate continues for up to 75 min in the presence of carbachol and declines rapidly when the muscarinic receptor antagonist atropine is added. Only when cells are treated with carbachol for 2.5 hr or longer is there a reduction in carbachol-stimulated phosphoinositide hydrolysis, and this is associated with a decrease in muscarinic receptor number. There does appear to be desensitization of hormone-stimulated Ca2+ mobilization in 1321N1 cells, because treatment of these cells with carbachol for 75 min leads to loss of the subsequent ability of carbachol to stimulate unidirectional 45Ca2+ efflux. Histamine-stimulated 45Ca2+ efflux also is lost in cells pretreated with carbachol, indicating that the desensitization is heterologous. We conclude that desensitization of hormone-stimulated, unidirectional 45Ca2+ efflux cannot be accounted for by a loss of receptor-mediated phosphoinositide hydrolysis. If phosphoinositide hydrolysis or inositol triphosphate formation are signals for calcium mobilization, the site at which the calcium response desensitizes must be distal to the initial receptor-mediated activation of phospholipase C.
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PMID:Agonist-induced desensitization of muscarinic receptor-mediated calcium efflux without concomitant desensitization of phosphoinositide hydrolysis. 298 82

Histamine stimulation of bovine adrenal medullary cells rapidly activated phospholipase C. [3H]Inositol 1,4,5-trisphosphate [[3H]Ins(1,4,5)P3] levels were transiently increased (200% of basal values between 1 and 5 s) before declining to a new steady-state level of approximately 140% of basal values. [3H]Inositol 1,4-bisphosphate [[3H]Ins(1,4)P2] content increased to a maximal and maintained level of 250% of basal values after 1 s, whereas levels of [3H]inositol 1,3,4-trisphosphate [[3H]Ins(1,3,4)P3], [3H]inositol 1,3-bisphosphate, and [3H]inositol 4-monophosphate ([3H]Ins4P) increased more slowly. The rapid responses were not reduced by the removal of extracellular Ca2+, but they were no longer sustained over time. The turnover rates of selected inositol phosphate isomers have been estimated in the intact cell. [3H]Ins(1,4,5)P3 was rapidly metabolized (t1/2 of 11 s), whereas the other isomers were metabolized more slowly, with t1/2 values of 113, 133, 104, and 66 s for [3H]Ins(1,3,4)P3, [3H]Ins(1,4)P2, an unresolved mixture of [3H]inositol 1- and 3-monophosphate ([3H]Ins1/3P), and [3H]Ins4P, respectively. The calculated turnover rate of [3H]Ins(1,4,5)P3 was sufficient to account for the turnover of the combination of both [3H]Ins(1,4)P2 and [3H]Ins(1,3,4)P3 but not that of [3H]Ins1/3P or [3H]Ins4P. These observations demonstrate that histamine stimulation of these cells results in a complex Ca(2+)-dependent and -independent response that may involve the hydrolysis of inositol phospholipids in addition to phosphatidylinositol 4,5-bisphosphate.
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PMID:Histamine-stimulated inositol phospholipid metabolism in bovine adrenal medullary cells: a kinetic analysis. 761 18

Histamine is a known chromaffin cell secretagogue that induces Ca(2+) -dependent release of catecholamines. However, conflicting evidence exists as to the source of Ca2+ utilized in histamine-evoked secretion. Here we report that histamine-H1 receptor activation induces redistribution of scinderin, a Ca(2+)-dependent F-actin severing protein, cortical F-actin disassembly, and catecholamine release. Histamine evoked similar patterns of distribution of scinderin and filamentous actin. The rapid responses to histamine occurred in the absence of extracellular Ca2+ and were triggered by release of Ca2+ from intracellular stores. The trigger for the release of Ca2+ was inositol 1,4,5-trisphosphate because U-73122, a phospholipase C inhibitor, but not its inactive isomer (U-73343), inhibited the increases in IP3 and intracellular Ca2+ levels, scinderin redistribution, cortical F-actin disassembly, and catecholamine release in response to histamine. Thapsigargin, an agent known to mobilize intracellular Ca2+, blocked the rise in intracellular Ca2+ concentration, scinderin redistribution, F-actin disassembly, and catecholamine secretion in response to histamine. Calphostin C and chelerythrine, two inhibitors of protein kinase C, blocked all responses to histamine with the exception of the release of Ca2+ from intracellular stores. This suggests that protein kinase C is involved in histamine-induced responses. The results also show that in the absence of F-actin disassembly, rises in intracellular Ca2+ concentration are not by themselves capable of triggering catecholamine release.
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PMID:Histamine-evoked chromaffin cell scinderin redistribution, F-actin disassembly, and secretion: in the absence of cortical F-actin disassembly, an increase in intracellular Ca2+ fails to trigger exocytosis. 764 7

In this study, we hypothesized that histaminergic increases in venular permeability result from a cascade triggered by activation of phospholipase C (PLC), inducing the synthesis of nitric oxide (NO) and activating guanylate cyclase. The apparent permeability coefficient to albumin (Pa) was measured in isolated porcine coronary venules subjected to constant flow and hydrostatic and oncotic pressures. Histamine (2.5, 5, and 10 microM) transiently and progressively increased Pa. The PLC inhibitor 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate (NCDC; 100 microM) decreased baseline permeability and abolished the effect of histamine. The NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 10 microM) and the guanylate cyclase inhibitor 6-anilinoquinoline-5,8-quinone (LY 83583; 10 microM) also blocked the histamine-induced hyperpermeability. L-Arginine (3 mM) reversed the inhibition by L-NMMA. NG-monomethyl-D-arginine did not influence the effect of histamine. Furthermore, sodium nitroprusside (10 microM) augmented Pa by two- to threefold; this effect was blocked in the presence of LY 83583 but not altered in the presence of NCDC. The results suggest that histamine increases coronary venular permeability by a direct action on the venular endothelial cells through a PLC-NO synthase-guanylate cyclase-signaling cascade.
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PMID:Histamine increases venular permeability via a phospholipase C-NO synthase-guanylate cyclase cascade. 768 77


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