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)

Membranes from human brain cortex (8-12 h post mortem) were labelled with [3H]inositol, in the presence of CMP, through the back reaction catalysed by PtdIns synthase. The enzyme incorporated [3H]inositol into phosphoinositides at a maximal rate of 419 pmol min-1 mg protein-1. In the absence of CMP, the labelling rate due to the PtdIns headgroup exchanging enzyme was 36 pmol min-1 mg protein-1. Human brain PtdIns synthase showed Kmapp values of 0.49 mM and 18 microM for inositol and CMP, respectively. In the presence of ATP, [3H]polyphosphoinositides formed after [3H]PtdIns were hydrolysed by phospholipase C in a GTP gamma S and neurotransmitter receptor agonist-dependent manner. Production of 3H-inositol phosphates as stimulated by GTP gamma S (350% of basal) was increased by the muscarinic agonists carbachol and oxotremorine-M (600% of basal) and by serotonin (485% of basal). The relative potencies of carbachol and oxotremorine-M were consistent with an action at muscarinic receptors. These results show that coupling between muscarinic and serotonin receptors and phospholipase C is preserved in membranes from post mortem human brain cortex and validate the use of a method involving direct [3H]inositol labelling of a membrane fraction to study the functional state of phospholipase C-coupled receptors in human brain samples.
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PMID:Neurotransmitter-stimulated breakdown of endogenous polyphosphoinositides in post mortem human brain. 791 14

The fourth member of mammalian beta-type phospholipase C isozymes, PLC-beta 4, was recently purified from bovine retina, and the corresponding cDNA was cloned from rat brain and sequenced. PLC-beta 4 has now been shown to differ from the other three mammalian beta-type isozymes (PLC-beta 1, -beta 2, and -beta 3) in that it is selectively inhibited by ribonucleotides. The inhibition requires the 5'-phosphate and 2'-hydroxyl groups of ribose as well as the base moiety. Thus, deoxyribonucleotides and ribose 5-phosphate were not inhibitory. The monophosphate, diphosphate, and triphosphate nucleoside derivatives were all inhibitory, whereas cyclic nucleotides were ineffective. Purine nucleotides were more potent inhibitors than pyrimidine nucleotides; the 50% inhibitory concentrations were 20-30 microM for AMP and GMP, and 100-200 microM for UMP and CMP. Unlike the other beta-type isozymes, PLC-beta 4 contains the GX4GKS consensus sequence for the recognition of the phosphoryl group of nucleotides. In the absence of ribonucleotides, the specific activity of PLC-beta 4 toward phosphatidyl-inositol 4,5-bisphosphate was four to five times the average specific activity of PLC-beta 1 and PLC-beta 3. Thus, nucleotide-dependent inhibition may serve to reduce the activity of PLC-beta 4 in the absence of a hormonal signal. The regulation of PLC-beta 4 by G-proteins was also studied. Similar to the other three PLC-beta isozymes, PLC-beta 4 was activated by the alpha subunit of Gq but not by the transducin alpha subunit. However, unlike other PLC-beta isozymes, PLC-beta 4 was not responsive to activation by G beta gamma subunits.
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PMID:Regulation of phospholipase C-beta 4 by ribonucleotides and the alpha subunit of Gq. 792 27

Previous studies have shown that in the neuroblastoma x glioma hybrid cell line NG108-15 lithium is able to induce an increase in diacylglycerol levels. This effect was shown to be enhanced by the presence of bradykinin. Another striking effect of lithium was a marked gain in the level of the liponucleotide phosphatidyl-CMP. Increased phosphatidyl-CMP levels were detected in the presence of lithium alone but were considerably more pronounced in the presence of both lithium and bradykinin. These results are consistent with the inhibitory action of lithium on key enzymes of the degradation pathway of inositol phosphates, resulting in a decrease in cellular inositol content and in an elevation in levels of phosphorylated inositols. Comparison of the mass of the inositol phosphates and diacylglycerol showed that the lithium-induced diacylglycerol levels were substantially greater than would be expected from phosphoinositide hydrolysis alone. One possible reason for the increase in the level of diacylglycerol through the action of lithium is the reversal of the reaction for the formation of phosphatidyl-CMP. The resulting phosphatidic acid would then need to be further dephosphorylated to diacylglycerol. The lithium-induced elevation of phosphatidyl-CMP was prevented by addition of myo-inositol (10-30 mM), suggesting that the increase in liponucleotide level was due to depletion of cellular inositol. Under the same conditions the elevated diacylglycerol concentration remained unchanged. Consequently, phosphatidyl-CMP is not its source, and diacylglycerol may arise through an effect of lithium on the degradation of phospholipids other than phosphoinositides. The action of phospholipase C or D on phosphatidylcholine is the most likely mechanism.
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PMID:Elevated phosphatidyl-CMP is not the source of diacylglycerol accumulation induced by lithium in NG108-15 cells. 843 63

The effect of lithium on inositol phospholipid resynthesis in primary cultures of cerebellar granule cells was studied. During activation of phospholipase C by the combined action of a muscarinic agonist and mild depolarization, the levels of inositol phospholipids as well as the inositol phospholipid precursor CMP-phosphatidate appeared highly sensitive to lithium with half-maximal accumulation of CMP-phosphatidate attained at 0.5 mM LiCl, a concentration close to that in the plasma of patients subjected to lithium therapy. Under the same conditions, the effect of lithium on inositol phospholipid metabolism appeared to be mediated by depletion of cytoplasmic free inositol content. This was indicated by the observation that preincubation for 48 h in high extracellular inositol concentrations could decrease or delay the depletion of inositol phospholipids and the accumulation of CMP-phosphatidate induced by 10 mM LiCl. Because even relatively high concentrations of extracellular inositol (500 microM) only partially prevented inositol phospholipid depletion, cerebellar granule cells appear to have a comparatively low capacity to accumulate inositol intracellularly, in comparison with other brain cells in culture. The relationship between CMP-phosphatidate accumulation and phospholipase C activity has also been investigated using a range of agonists that have been reported to act on cerebellar granule cells.
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PMID:Characterization of the effects of lithium and inositol on phosphoinositide turnover in cerebellar granule cells in primary culture. 859 21

1. The relationship between muscarinic receptor activation, phosphoinositide turnover, calcium mobilisation and M-current inhibition has been studied in rat superior cervical ganglion (SCG) neurones in primary culture. 2. Phosphoinositide-specific phospholipase C (PLC) stimulation was measured by the accumulation of [3H]-cytidine monophosphate phosphatidate (CMP-PA) after incubation with [3H]-cytidine in the presence of Li+. The muscarinic agonist oxotremorine methiodide (oxo-M) stimulated PLC in a dose-dependent manner with an EC50 of approximately 3.5 microM. 3. The concentration-response curve for oxo-M was shifted to the right by a factor of about 10 by pirenzepine (100 nM), suggesting a pKB (-log of the apparent dissociation constant) of 7.9 +/- 0.4, while himbacine (1 microM) shifted the curve by a factor of about 13 (pKB approximately 7.1 +/- 0.6). This indicates involvement of the M1 muscarinic receptor in this response. 4. The accumulation of CMP-PA was localised by in situ autoradiography to SCG principal neurones, with no detectable signal in glial cells present in the primary cultures. 5. The ability of oxo-M to release Ca2+ from inositol(1,4, 5)trisphosphate (InsP3)-sensitive stores was determined by fura-2 microfluorimetry of SCG neurones voltage clamped in perforated patch mode. Oxo-M failed to evoke intracellular Ca2+ (Ca2+i) mobilisation in SCG neurones voltage clamped at -60 mV, but produced a significant Ca2+i rise (67 +/- 15 nM, n = 9) in cells voltage clamped at -25 mV. 6. Thapsigargin (0.5-1 microM) caused a 70 % inhibition of the oxo-M-induced Ca2+i increase, indicating its intracellular origin, while oxo-M-induced inhibition of M-current in the same cells was unaffected by thapsigargin. 7. Our results do not support the involvement of InsP3-sensitive calcium mobilisation in M-current inhibition.
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PMID:Muscarinic M1 receptors activate phosphoinositide turnover and Ca2+ mobilisation in rat sympathetic neurones, but this signalling pathway does not mediate M-current inhibition. 1051 4

A dense glycocalix covers the surface of Trypanosoma cruzi, the agent of Chagas disease. Sialic acid in the surface of the parasite plays an important role in the infectious process, however, T. cruzi is unable to synthesize sialic acid or the usual donor CMP-sialic acid. Instead, T. cruzi expresses a unique enzyme, the trans-sialidase (TcTS) involved in the transfer of sialic acid from host glycoconjugates to mucins of the parasite. The mucins are the major glycoproteins in the insect stage epimastigotes and in the infective trypomastigotes. Both, the mucins and the TcTS are anchored to the plasma membrane by a glycosylphosphatidylinositol anchor. Thus, TcTS may be shed into the bloodstream of the mammal host by the action of a parasite phosphatidylinositol-phospholipase C, affecting the immune system. The composition and structure of the sugars in the parasite mucins is characteristic of each differentiation stage, also, interstrain variations were described for epimastigote mucins. This review focus on the characteristics of the interplay between the trans-sialidase and the mucins of T. cruzi and summarizes the known carbohydrate structures of the mucins.
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PMID:Trans-sialidase and mucins of Trypanosoma cruzi: an important interplay for the parasite. 2164 82


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