Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the polyamine, spermidine, on formyl-methionyl-leucyl-phenylalanine stimulated hydrolysis of polyphosphoinositides was examined in purified human neutrophils by measurement of inositol phosphate production from radioactively labelled inositol. Spermidine inhibited formyl-methionyl-leucyl-phenylalanine stimulated inositol phosphate production by neutrophil in a dose dependent manner. Inhibition of formyl-methionyl-leucyl-phenylalanine stimulated inositol phosphate accumulation by spermidine was maximal at 10 microM and the IC50 value for this effect was 4.2 microM spermidine. This action of spermidine, thought to be mediated by a membrane component other than phospholipase C, may reflect a control mechanism modulating the response of the polyphosphoinositide system.
 ...
PMID:Inhibitory action of spermidine on formyl-methionyl-leucyl-phenylalanine stimulated inositol phosphate production in human neutrophils. 303 76

The endogenous polyamines spermidine and spermine enhanced guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S)-stimulated phosphoinositide turnover with EC50 values of 100 +/- 30 and 50 +/- 15 microM, respectively, whereas the synthetic polyamines N,N'-bis(3-aminopropyl)-1,3-propanediamine and -ethylenediamine inhibited GTP-gamma-S-stimulated phosphoinositide turnover, with maximal inhibition at 1 mM. Kinetic analysis of GTP-gamma-S-stimulated phosphoinositide turnover in the absence and presence of spermidine showed that the Km for GTP-gamma-S was not changed (1,303 +/- 270 and 1,069 +/- 214 nM, respectively), whereas the Vmax was increased by 206% (1,566 +/- 141 and 4,792 +/- 84 cpm, respectively), indicating that spermidine and GTP-gamma-S acted at different sites. Spermidine also enhanced Ca(2+)-stimulated phosphoinositide turnover in the absence of GTP-gamma-S by decreasing the Ca2+ requirement of the phosphoinositide-specific phospholipase C. Arcaine and agmatine, polyamine antagonists at the NMDA receptor complex, did not block the effects of spermidine on GTP-gamma-S- and Ca(2+)-induced phosphoinositide turnover, suggesting that the spermidine effects are not mediated through these specific polyamine sites. Furthermore, spermidine increased the level of [3H]phosphatidylinositol 4-phosphate (EC50 = 120 +/- 10 microM), without affecting significantly the levels of [3H]-phosphatidylinositol and [3H]phosphatidylinositol 4,5-bis-phosphate. Collectively these data indicate that the enhanced phosphoinositide turnover induced by spermidine in the presence of GTP-gamma-S or Ca2+ is mediated through multiple levels of the phosphoinositide turnover cascade.
 ...
PMID:Regulation of the phosphoinositide cascade by polyamines in brain. 793 Dec 84

Congenital defects in platelet function are associated with bleeding manifestations of variable intensity and arise by diverse mechanisms. Defects in platelet-vessel wall interaction (disorders of adhesion) may arise because of qualitative or quantitative abnormalities in plasma von Willebrand factor (von Willebrand disease) or in platelet glycoprotein Ib, the binding site on platelets for von Willebrand factor (Bernard-Soulier syndrome). Disorders characterized by abnormal platelet-platelet interaction (disorders of aggregation) arise because of absence of plasma fibrinogen (congenital afibrinogenemia) or because of qualitative or quantitative abnormalities in platelet glycoprotein IIb-IIIa complex (Glanzmann's thrombasthenia). Patients with abnormalities in platelet secretion and signal transduction are a heterogeneous group characterized by impaired aggregation responses and secretion of granule contents. A small proportion of these patients have deficiency of granule stores (storage pool deficiency [SPD]) or impaired production of thromboxane A2; in most, the mechanisms underlying the platelet dysfunction are unknown. Evidence is accumulating that at least some patients have abnormalities in early signal transduction events. Abnormalities in phospholipase C activation, G-protein activation, and other events (eg, protein phosphorylation) have been documented. Platelets play a major role in blood coagulation, and in Scott syndrome, there is an abnormality in platelet contribution to the mechanisms leading to thrombin generation. In most patients with inherited platelet dysfunction, the underlying mechanisms remain to be delineated. Future studies of these patients should yield valuable new information on normal platelet mechanisms.
 ...
PMID:Congenital disorders of platelet function: disorders of signal transduction and secretion. 970 60

In Cantharanthus roseus transformed roots, the application of methylglyoxal bis(guanylhydrazone) (MGBG), an inhibitor of S-adenosylmethionine decarboxylase (SAMDC; EC 4.1.1.50), inhibited the root growth in a dose-dependent manner with a DL(50) of about 300 micro m. Spermidine and spermine (Spm) levels and SAMDC and phospholipase C (PLC; EC 3.1.4.3) activities were reduced in the presence of the inhibitor. The inhibition was reversed by the addition of Spm. Radioactivity from [(14)C]Spm was detected in an immunoprecipitated fraction with an antibody anti-PLC-delta. To our knowledge, this is the first direct evidence that demonstrates an interaction of Spm with the signal transduction cascade phosphoinositide-Ca(2+).
 ...
PMID:Interaction of spermine with a signal transduction pathway involving phospholipase C, during the growth of Catharanthus roseus transformed roots. 1503 86

Prostaglandins exert their effects on target cells by coupling to specific G protein-coupled receptors (GPCRs) that are often co-expressed in the same cells and use alternate and in some cases opposing intracellular signaling pathways. This study investigated the cross-talk that influences intracellular signaling and gene expression profiling in response to co-activation of the EP2 and FP prostanoid receptors in Ishikawa cells stably expressing both receptors (FPEP2 cells). In this study we show that in FPEP2 cells, PGF alone does not alter adenosine 3',5'-cyclic monophosphate (cAMP) production, but in combination with Butaprost enhances EP2 receptor mediated cAMP release compared to treatment with Butaprost alone. PGF-mediated potentiation of cAMP release was abolished by antagonism of the FP receptor, inhibition of phospholipase C (PLC) and inositol phosphate receptor (IP3R) whereas inhibition of protein kinase C (PKC) had no effect. Moreover, inhibition of calcium effectors using calmodulin antagonist (W7) or Ca(2+)/calmodulin-dependent kinase II (CaMK-II) inhibitor (KN-93) abolished PGF potentiation of Butaprost-mediated cAMP release. Using siRNA molecules targeted against the adenylyl cyclase 3 (AC3) isoform, we show that AC3 is responsible for the cross-talk between the FP and EP2 receptors. Using gene array studies we have identified a candidate gene, Spermidine/N1-acetyltransferase (SAT1), which is regulated by this cAMP mediated cross-talk. In conclusion, this study demonstrates that co-activation of the FP and EP2 receptors results in enhanced release of cAMP via FP receptor-G alpha(q)-Ca(2+)-calmodulin pathway by activating calcium sensitive AC3 isoform.
 ...
PMID:EP2 receptor mediated cAMP release is augmented by PGF 2 alpha activation of the FP receptor via the calcium-calmodulin pathway. 1978 48