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)

In pancreatic islets the bulk of phosphoinositide-specific phospholipase C (PI-PLC) activity was cytosolic. The soluble enzyme was activated by submicromolar concentrations of Ca2+, independent of calmodulin. It was unaffected by glucose and a series of glycolytic intermediates, including glyceraldehyde 3-phosphate. These observations lend support to the hypothesis that glucose-stimulated inositol triphosphate production in islets may be secondary to and provoked by glucose-mediated Ca2+ influx. All four pyridine nucleotides stimulated PI-PLC. Phosphatidylinositol hydrolysis was also stimulated by dioleine and arachidonic acid, and by the polyamines, putrescine and spermine. Phosphatidylinositol hydrolysis was inhibited by chlorpromazine, tetracaine, ATP, 5'-AMP, inorganic pyrophosphate and by phosphatidylinositol 4,5-bisphosphate, phosphatidylcholine and phosphatidylserine--but not affected by phosphatidylethanolamine. The cyclic nucleotides, cAMP and cGMP had no effect on the enzyme, and GTP-gamma-S did not activate the enzyme event at very low Ca2+ concentrations. The diglyceride lipase inhibitor, RHC 80267, and the cyclooxygenase inhibitor, indomethacin, had no effect on PI-PLC activity.
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PMID:Characteristics of phosphoinositide-specific phospholipase C activity from mouse pancreatic islets. 166 77

Mesangial cells are contractile pericytes of the kidney glomerulus. Mesangial contraction/relaxation contributes to the regulation of glomerular hemodynamics. Additionally, mesangial cells process filtered macromolecules, synthesize extracellular matrix, respond to and release a number of cytokines and vasoactive mediators. Cultured mesangial cells express receptors for circulating and local agents that affect glomerular function. These receptors are coupled to distinct signaling pathways, namely phospholipase C and A2, transducing vasoconstrictor stimuli, and adenylate/guanylate cyclase, transducing vasodilators. Early intracellular signals include changes of cytosolic ions and cyclic nucleotides. They translate into short-term responses, such as cell depolarization and contraction, and later events, such as prostanoid synthesis and cell proliferation. Studies of mesangial cell behavior in culture may largely enhance our current understanding of glomerular pathophysiology.
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PMID:Cellular basis of hormonal actions in the glomerulus. 217 48

The effects of adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP) and phorbol 12,13 dibutyrate (PDBu) on the Ca2+ sensitivity of the contractile elements in the rat mesenteric artery were investigated, using a method of permeabilizing smooth muscle with Staphylococcal alpha-toxin. Both cAMP and cGMP relaxed the permeabilized rat mesenteric artery at the intracellular Ca2+ concentrations [( Ca2+]i) held constant with Ca2+ EGTA buffer and Ca2+ ionophore, ionomycin. In addition, forskolin and sodium nitroprusside which activate adenylate and guanylate cyclases, respectively, also induced relaxation at a fixed [Ca2+]i. In contrast PDBu which stimulates protein kinase C caused an increase in force at a constant [Ca2+]i which could be partially reversed by cAMP or cGMP. These results indicate that second messengers exert direct control over smooth muscle Ca2+ sensitivity of the contractile elements, which is of physiologic and pharmacologic importance.
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PMID:Direct regulation of smooth muscle contractile elements by second messengers. 255 Dec 77

Enhancement by thrombin of Ca2+-dependent 5HT secretion in the absence of added GTP decreases as the time between electropermeabilisation and addition of thrombin is increased. No decrease occurs if thrombin is added with GTP. Observation of apparent GTP-independent receptor/phospholipase C coupling may result from the presence of bound GTP in the preparation. Enhancement by GTP of Ca2+-dependent 5HT secretion occurs with a significant lag indicating an agonist-independent effect. Cyclic 3'5'-AMP inhibits enhancement by GTP of Ca2+-dependent 5HT secretion while having no effect on enhancement induced by GTP gamma S. Hence cyclic AMP may impair receptor/phospholipase C coupling by enhancing Np GTPase activity.
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PMID:Secretion of 5-hydroxytryptamine from electropermeabilised human platelets. Effects of GTP and cyclic 3',5'-AMP. 282 80

Incubation of [3H] inositol-labeled cultured rat aortic vascular smooth muscle cells with angiotensin II caused the dose- and time-dependent formation of inositol mono-, bis- and trisphosphates. Under these conditions, adenosine triphosphate (ATP) stimulated the formation of these inositol phosphates. The maximal reaction velocities obtained by ATP and angiotensin II were roughly the same. The doses of ATP giving half maximal and maximal reaction velocities were about 100 microM and 1 mM, respectively. This action of ATP was mimicked by other nucleotides such as adenosine diphosphate (ADP) and guanosine triphosphate (GTP), but these nucleotides were far less effective than ATP. Adenosine monophosphate (AMP), adenosine, guanosine diphosphate (GDP), guanosine monophosphate (GMP), deoxythymidine trisphosphate (dTTP), and cytosine triphosphate (CTP) were almost ineffective. The formation of inositol phosphates induced by ATP was inhibited partially by pretreatment of the cells with pertussis toxin. This toxin ADP-ribosylated a protein with a molecular mass of about 40,000. These results indicate that ATP induced the phospholipase C-mediated hydrolysis of phosphoinositides probably via P2-purinoceptors in rat aortic vascular smooth muscle cells, and suggest that a pertussis toxin-sensitive GTP-binding protein is involved at least partially in the coupling of this receptor to the phospholipase C in this cell type.
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PMID:Stimulation of phospholipase C-mediated hydrolysis of phosphoinositides by adenosine 5'-triphosphate via P2-purinoceptors in cultured rat aortic vascular smooth muscle cells. 284 65

Various regulators of protein kinase activities were tested for their effects on the in vitro transfer of phosphate from [gamma-32P]ATP to four proteins of rat brain synaptic particulate preparations. One protein, of apparent molecular weight 44,000, accepted 32P in the presence of 8 mM EDTA and no added Mg2+. It was the major phosphoprotein of brain mitochondria. Its phosphorylation was inhibited by pyruvate and stimulated by K+, and it comigrated in electrophoretic gels with authentic alpha-subunit of pyruvate: lipoamide oxidoreductase (decarboxylating) (EC 1.2.4.1) from bovine heart. The major kinase acting on three proteins of apparent molecular weights 24,000, 21,000, and 19,000 was stimulated by Ca2+, by preincubation with phospholipase C, and by 12-tetradecanoyl 4-beta-phorbol 13-acetate. Phosphorylation of these lower-molecular-weight proteins was inhibited by ACTH1-24, by cyclic 3',5'-adenosine monophosphate, and by 50 microM trifluoperazine. The stimulatory effect of Ca2+ was antagonized by calmodulin. The kinase in question appears to be B-50 protein kinase or protein kinase C.
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PMID:Regulation of phosphate incorporation into four brain phosphoproteins that are affected by experience. 298 Dec 89

We present evidence which indicates that highly purified placental acid sphingomyelinase hydrolyses [14C]phosphatidylcholine [( 14C]PC) and the synthetic phosphodiester 4-methylumbelliferyl phosphorylcholine (4-MUPC). Hydrolysis was achieved by phospholipase C phosphodiesterase action. Of the several detergents tested, sodium taurocholate alone was necessary for PC hydrolysis, while 4-MUPC was hydrolysed independent of any detergent requirement. The pH optima for the reactions were 4.6-4.8 for PC hydrolysis and 4.8-5.0 for 4-MUPC hydrolysis. As with sphingomyelin hydrolysis, degradation of both PC and 4-MUPC was inhibited by 5'-, 3'-, and 2'-AMP, 5'-AMP being the most effective of the three. Furthermore, the phosphodiesterase activity against PC and 4-MUPC copurified with sphingomyelinase from human placenta and cross-reacted with a specific anti-sphingomyelinase monoclonal antibody, strongly indicating identity of the phosphodiesterases. This explains phospholipase C deficiency in sphingomyelinase-deficient Niemann-Pick disease cells.
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PMID:Phosphatidylcholine and 4-methylumbelliferyl phosphorylcholine hydrolysis by purified placental sphingomyelinase. 299 Jun 45

The arachidonate inhibition of the adenylate-cyclase system of cultured pig thyroid cells was not mediated by cyclooxygenase, lipoxygenase or peroxidase metabolites. Indeed ETYA, an inhibitor of cyclooxygenase and lipoxygenase, and methimazole, an inhibitor of peroxidase and iodination were without effect on the arachidonate inhibition. Moreover the effect of arachidonate was amplified by a combination with ETYA. In 32P incorporation experiments we observed a modification of the labelling of individual phospholipids of cultured pig thyroid cells resulting in a decrease into phosphatidylinositol (PI) and an increase into phosphatidate (PA) of arachidonate and ETYA-treated cells. These results may be explained by an inhibition of CDP-diacylglycerol: inositol transferase and conversely a stimulation of PI specific phospholipase C yielding a decrease in PI and an increase in PA, which inhibits in turn adenylate cyclase activity possibly by Ca2+ translocation.
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PMID:Effects of eicosatetraynoic acid (ETYA) on cultured pig thyroid cells. Relationships between the inhibition of the phosphatidate-phosphatidyl inositol cycle, the iodination and the cyclic AMP responsiveness to thyrotropin. 618 61

Previous studies have indicated different energy requirements for some platelet responses; these differences could, however, be due to inadequate methodology and differences in platelet preparation. The present study describes the effect of decreasing ATP availability on seven platelet responses measured in gel-filtered human platelets. The cells, prelabelled with 5-hydroxy[(3)H]tryptamine, [(3)H]- or [(14)C]adenine, [(32)P]P(i) or [(3)H]arachidonate, were incubated with antimycin A and 2-deoxy-d-glucose. Platelet responses induced by thrombin and collagen (secretion only), level of metabolic ATP and the adenylate energy charge (AEC) were determined at various times during incubation. Platelet aggregation was rapidly inhibited after a lag of 5-15 min and with 50% inhibition at AEC = 0.55-0.60. Secretion of 5-hydroxy[(14)C]tryptamine and ATP + ADP from dense granules and of fibrinogen and beta-thromboglobin from alpha-granules were inhibited in parallel, without a lag and with 50% inhibition at AEC = 0.65-0.70. The inhibition of secretion of platelet factor 4 from the alpha-granules followed another pattern with 50% inhibition at AEC = 0.70-0.80. Breakdown of [(3)H]-phosphatidylinositol, formation of [(3)H]- and [(32)P]-phosphatidate, liberation of [(3)H]arachidonate and secretion of acid hydrolases were inhibited in parallel and inhibition was present at the start of incubation with 50% inhibition at AEC = 0.80-0.87. These results suggest that the responses have different energy requirements, increasing in the order: aggregation < dense granule and alpha-granule secretion < acid hydrolase secretion, phosphatidylinositol breakdown, phosphatidate formation and arachidonate liberation. The powerful inhibition of phosphatidylinositol breakdown by metabolic inhibitors suggests that energy-requiring steps are involved in the activation of phospholipase C.
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PMID:Differential energy requirements for platelet responses. A simultaneous study of aggregation, three secretory processes, arachidonate liberation, phosphatidylinositol breakdown and phosphatidate production. 621 2

Hydrolysis of 2-[1-14C]oleoyl phosphatidylcholine and of 1-[1-14C]oleoyl lysophosphatidylcholine by lysosomes prepared from rat liver using Triton WR-1339 has been studied. At pH 5.0 sodium taurocholate stimulated the release by the soluble lysosomal fraction of labelled lysophosphatidylcholine, diacyl- and monoacylglycerol and fatty acids from [14C]phosphatidylcholine. The time course of appearance of labelled products suggested that monoacylglycerol could be released as a result of the action of phospholipase A1 followed by lysophospholipase C or by the initial action of phospholipase C followed by monoacylglycerol lipase. The hydrolysis of 1-[14C]acyl lysophosphatidylcholine was also stimulated by sodium taurocholate under similar conditions; however, only release of monoacylglycerol was increased, whereas release of fatty acid was inhibited. Mg2+ inhibited the release of labelled monoacylglycerol and of fatty acid from lysophosphatidylcholine. The detergents deoxycholate and Triton X-100 and phospholipids were strongly inhibitory. 5'-AMP almost completely suppressed release of monoacylglycerol but increased release of fatty acid. Chloroquine strongly suppressed release of monoacylglycerol and only at high concentration (1.25 mM) diminished fatty acid release. In the presence of sodium taurocholate the predominant mechanism for degradation of phosphatidylcholine by the soluble fraction of lysosomes involves phospholipase A followed by phospholipase C. Assay of release of monoacylglycerol from [14C]lysophosphatidylcholine catalyzed by extracts of fibroblasts from patients with Niemann-Pick disease and controls in the presence of taurocholate revealed that lysophospholipase C activity was lacking in those cell lines that were deficient in sphingomyelinase. This suggests that lysophospholipase C and sphingomyelinase activities may be catalyzed by one enzyme.
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PMID:Degradation of lysophosphatidylcholine by lysosomes. Stimulation of lysophospholipase C by taurocholate and deficiency in Niemann-Pick fibroblasts. 673 21


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