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)

The activity of phospholipase C acting against [3H]-inositol-phosphatidylinositol (PI) and the activity of arachidonic acid (AA) release from [1-14C]arachidonoyl-phosphatidylinositol by enzyme(s) located in synaptic vesicles (SV) isolated from normoxic and ischemic brains was investigated. Brain ischemia significantly activated phospholipase C (PhLC) by about 90% and AA release by about 50%. PhLC and AA release in SV isolated from brain submitted to ischemia were not further activated by 2 mM CaCl2 contrary to the enzymes from normoxic brain. The activation of PhLC and PhLA2 may produce conformational changes and rearrangement of the SV membranes leading to vesicle-membrane fusion and subsequently to massive neurotransmitter release known to occur during ischemia.
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PMID:Synaptic vesicle-bound phospholipase(s) acting on phosphatidylinositol exhibit(s) high susceptibility to brain ischemia. 211 86

We tested the contribution of extracellular calcium (Ca2+) to membrane electrical responses to acetylcholine (ACh) in native Xenopus oocytes. Removal of Cao caused a decrease in both the rapid (D1) and the slow (D2) chloride currents that comprise the common depolarizing response to ACh in native oocyte. The effect of Ca2+o removal on the muscarinic response was mimicked by the addition of 1 mM Mn2+, an effective antagonist of calcium influx, though not by antagonists of voltage-sensitive calcium channels. When oocytes were challenged with ACh in Ca2(+)-free medium, subsequent addition of 1.8 mM CaCl2 resulted in a rapid, often transient, depolarizing current. Similarly to the Ca2+o-dependent component of membrane electrical responses, the Ca2(+)-evoked current was reversibly abolished by Mn2+, though not by antigonists of voltage-sensitive calcium channels. Depletion of cellular calcium potentiated the Ca2(+)-evoked current, implying negative feedback of calcium channels by calcium. Injection of 10-100 fmol of inositol 1,4,5-trisphosphate (IP3) resulted in a two-component depolarizing current. IP3 injection promoted the appearance of Ca2+o-evoked current that was significantly potentiated by previous calcium depletion. We suggest that activation of cell-membrane muscarinic receptors causes opening of apparently voltage-insensitive and verapamil or diltiazem-resistant calcium channels. These channels may be activated by IP3 or its metabolites, which increase following the activation of cell membrane receptors coupled to a phospholipase C. The channels may be identical to receptor-operated channels described in other model systems.
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PMID:Extracellular calcium participates in responses to acetylcholine in Xenopus oocytes. 215 9

The effect of fluoride (NaF; 10 mM sodium fluoride plus deferoxamine to chelate contaminating aluminum) and fluoride plus aluminum fluorides (AlF; 10 mM sodium fluoride plus 20 microM aluminum chloride) on activation of rabbit femoral arteries was investigated. AlF and NaF produced large increases in stress (force/muscle cross-sectional area), but temporal changes were dissimilar, as were other indices of muscle activation. Stress produced by NaF developed slowly and only after a long delay of about 15 min, whereas stress produced by AlF developed rapidly after a delay of only about 5 min. NaF-induced contractions were more sustained than AlF-induced contractions. Both AlF and NaF increased the level of cross-bridge phosphorylation and the velocity of muscle shortening, but at comparable stresses, AlF produced greater increases than did NaF. AlF produced a large increase in lP production, whereas NaF produced a small increase. Also, AlF-induced stress was largely insensitive to inhibition by the calcium channel blocker, nifedipine (1 microM), whereas NaF-induced stress was largely inhibited by nifedipine. However, in tissues depleted of calcium, both agents produced potent contractions when CaCl2 was added back to the tissues (EC50 values for AlF, NaF, histamine, phenylephrine and KCl were, respectively, 0.057, 0.085, 0.11, 0.11 and 0.23 mM). AlF, but not NaF, strongly desensitized arteries to phenylephrine, causing a 73% reduction in the ability of phenylephrine to achieve maximum steady-state stress. These data suggest that fluoride contracted rabbit femoral arteries by stimulating L-type calcium channels, and that aluminum fluoride stimulated phospholipase C, producing additional muscle activation.
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PMID:Differential activation of rabbit femoral arteries by aluminum fluoride and sodium fluoride. 216 93

Release of arachidonic acid (AA) from 1-stearoyl-2-[14C]arachidonyl-glycerophosphoinositol (PI) by plasma membrane-bound enzyme(s) is a calcium-dependent reaction and is markedly activated at 4 x 10(-4) M CaCl2. In the presence of Ca2+, the agonist of the cholinergic receptor (carbachol) enhances, in a dose-related manner, AA release. Moreover, GTP and its non-hydrolysable analogs GTP gamma S and GppNHp and also NaF additionally increase the carbachol-mediated liberation of AA from PI. On the contrary, in the absence of Ca2+ carbachol and GTP gamma S have no stimulatory effect on AA release. Guanosine-5'-O-2-thiodiphosphate GDP gamma S, which inhibits the function of GTP-binding proteins, also suppresses carbachol-mediated activation of AA release from PI. The stimulatory effect of carbachol and guanine nucleotides was observed exclusively in the brain plasma membrane (there was no effect on mitochondria, microsome and cytosolic enzymes). Quinacrine, the inhibitor of phospholipase A2, completely inhibits carbachol- and guanine nucleotide-activated AA release and greatly (by about 60-70%) decreases Ca(2+)-dependent AA liberation from phosphatidylinositol. These results indicate that GTP-binding protein(s) are involved in the regulation of carbachol-mediated AA release. The main pool of this acid is liberated from phosphatidylinositol by phospholipase A2 and only a small pool of AA may be released indirectly as the result of PI hydrolysis by sequential action of phospholipase C and diacylglycerol lipase.
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PMID:Guanine nucleotides and fluoride enhance carbachol-mediated arachidonic acid release from phosphatidylinositol. Evidence for involvement of GTP-binding protein in phospholipase A2 activation. 251 94

The effect of 10 min ischemia on the activity of phospholipase C acting against [3H]inositol-phosphatidylinositol (PI) and [3H]inositol-phosphatidylinositol 4,5-bisphosphate (PIP2) in the brain subsynaptosomal fractions was investigated. In the presence of endogenous CaCl2, specific activity of phospholipase C acting on phosphatidylinositol was as follows: synaptic cytosol (SC) greater than synaptic vesicles (SV) greater than synaptic plasma membrane SPM). Brain ischemia activated phospholipase C acting on PI by about 60% and 40% in SV and SPM, respectively. The enzyme of synaptic cytosol was not affected by ischemic insult. Phospholipase C acting against PIP2 in the presence of endogenous calcium expressed the specific activity in the following order: SV greater than SPM greater than SC. After 10 min of brain ischemia, activity of phospholipase C acting on PIP2 was significantly suppressed in all subsynaptosomal fractions by about 50-60%. These results indicate that prolonged ischemia produced activation exclusively of phospholipase C acting against phosphatidylinositol.
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PMID:Prolonged ischemia differently affects phospholipase C acting against phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate in brain subsynaptosomal fraction. 255 83

Brush-border membrane vesicles were prepared from rat kidney cortex by Mg precipitation. Using quin2 (free acid), intravesicular [Ca2+] was found to be 44 microM and less than 300 nM when vesicles were incubated in 0.2 mM CaCl2 or Ca-free buffer, respectively. In Ca-loaded vesicles, the initial D-glucose uptake, measured in the presence of 150 mM Na+ and 0.1 mM D-glucose inward gradients, was reduced to 30% of the control uptake. This reduction persisted when the extra-vesicular Ca2+ was chelated by ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid but was abolished in the presence of saturating concentrations of D-glucose. Whereas KG0.5 (g) for D-glucose at constant [Na] in the Ca-loaded membranes increased by approximately 50% of the control value (0.5 +/- 0.1 mM), no significant change in Jmax was observed. In contrast, both Jmax and KG0.5 (Na) for glucose, measured as a function of [Na] in the extravesicular fluid, were found to be significantly reduced. Na uptake, determined in the presence of 0.5 mM amiloride, was found to increase by approximately 30% of the value for control membrane. This increase was abolished when vesicles were preincubated with 0.5 mM neomycin or 0.5 mM phlorizin. The results suggest that the effect of Ca2+ on Na entry may be mediated in part by activation of phospholipase C and are consistent with a model of cotransport in which Ca2+ increases the mobility of the binary Na-sugar-translocator complex, thus leading to uncoupling of Na transport from glucose uptake ("slipping") and in part with Ca-induced Na entry by nonmediated leakage.
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PMID:Effect of Ca on Na-D-glucose cotransport across isolated renal brush-border membranes. 275 Sep 17

It has recently been appreciated that thrombin induces the retraction of endothelial cells resulting in an alteration of the integrity of the monolayers. We studied thrombin-induced changes in cytosolic calcium concentration (Ca2+i) using microfluorometry of fura-2-loaded single cells, cell topography (scanning electron microscopy), and cytoskeleton (rhodamine phalloidin) in endothelial cells. Thrombin caused an initial and sustained phase of an increase in Ca2+i. Pretreatment with pertussis toxin abolished both phases of Ca2+i response. Sustained phase of thrombin effect required extracellular calcium. Pretreatment of endothelial cells with indomethacin protracted the sustained phase, whereas a lipoxygenase inhibitor, nordihydroguaiaretic acid curtailed it. Thrombin caused a marked retraction of confluent endothelial cells coincident with the sustained phase of Ca2+i response. This was paralleled by the formation of gaps in F-actin distribution at the periphery of the cells. Pretreatment of endothelial cells with nordihydroguaiaretic acid blunted the thrombin-induced cell retraction. Microinjection of various putative messengers into the endothelial cells showed that initial Ca2+ mobilization is not sufficient to account for sustained elevation of Ca2+i. The sustained response required microinjection of phospholipase A2 or co-injection of phospholipase A2 with phosphatidylinositol 4,5-bisphosphate-specific phospholipase C, phosphatidylinositol 1,4,5-trisphosphate, or CaCl2, further implying that thrombin receptor(s) can be coupled to both phospholipases C and A2. Sustained elevation of Ca2+i was a necessary prerequisite for the thrombin-induced changes in endothelial cell topography.
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PMID:Nature of thrombin-induced sustained increase in cytosolic calcium concentration in cultured endothelial cells. 277 5

Evidences have been provided in our laboratory that in neutrophils different signal transduction sequences for the activation of O2(-)-forming NADPH oxidase can be triggered by the same stimulus (Biochem. Biophys. Res. Commun. 1986, 135, 556-565; 1986, 135, 785-794; 1986, 140, 1-11). The results presented here show that the transduction sequence triggered by fluoride via dissociation of G-proteins and involving messengers produced by stimulation of phosphoinositide turnover, Ca2+ changes and translocation of protein kinase C from the cytosol to the plasmamembrane, can be bypassed when a primed state of neutrophils is previously induced. In fact: i) fluoride causes a pertussis toxin insensitive and H-7 sensitive respiratory burst in human neutrophils, which is linked to the activation of hydrolysis of PIP2, rise in [Ca2+]1 and translocation of PKC. In Ca2+-depleted neutrophils these responses to fluoride do not occur and are restored by addition of CaCl2. ii) The pretreatment of Ca2+-depleted unresponsive neutrophils with non stimulatory doses of PMA restores the activation of the NADPH oxidase by fluoride but not the turnover of phosphoinositides and PKC translocation. The nature of the alternative transduction sequence, the reactions different from phospholipase C activated by G-protein for the alternative sequence and the role of these discrete pathways for NADPH oxidase activation are discussed.
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PMID:Fluoride can activate the respiratory burst independently of Ca2+, stimulation of phosphoinositide turnover and protein kinase C translocation in primed human neutrophils. 282 1

Bacillus cereus secretes phospholipases C, which hydrolyze phosphatidylcholine, sphingomyelin and phosphatidylinositol. A 7.5-kb HindIII fragment of B. cereus DNA cloned into Escherichia coli, with pUC18 as a vector, directed the synthesis of the sphingomyelin-hydrolyzing phospholipase C, sphingomyelinase. Nucleotide sequence analysis of the subfragment revealed that it contained two open reading frames in tandem. The upstream truncated open reading frame corresponds to the carboxy-terminal portion of the phosphatidylcholine-hydrolyzing phospholipase C, and the downstream open reading frame to the entire translational portion of the sphingomyelinase. The two phospholipase C genes form a gene cluster. As inferred from the DNA sequence, the B. cereus sphingomyelinase has a signal peptide of 27 amino acid residues and the mature enzyme comprises 306 amino acid residues, with a molecular mass of 34233 Da. The signal peptide of the enzyme was found to be functional in protein transport across the membrane of E. coli. The enzymatic properties of the sphingomyelinase synthesized in E. coli resemble those of the donor strain sphingomyelinase. The enzymatic activity toward sphingomyelin was enhanced 20-30-fold in the presence of MgCl2, and the adsorption of the enzyme onto erythrocyte membranes was accelerated in the presence of CaCl2.
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PMID:Nucleotide sequence and expression in Escherichia coli of the gene coding for sphingomyelinase of Bacillus cereus. 284 Nov 28

When the phorbol ester, 4 beta-phorbol-12-myristate-13-acetate (PMA) or bacterial phospholipase C (PL-C) is added to a preparation of purified adult rat Leydig cells, containing 2 mM CaCl2, a time- and dose-dependent decreases of LH-stimulated testosterone production is observed. After a 3 h stimulation with oLH (100 ng/ml), PMA (100 ng/ml) and PL-C (1.6 U/ml) do not affect the cell viability or the hCG specific binding, while cAMP accumulation is significantly reduced; cAMP-stimulated steroidogenesis is diminished only in the presence of PL-C. These observations suggest that in vitro: (i) activated Ca2+- and phospholipid-dependent protein kinase is implicated in the regulation of rat Leydig cell steroidogenesis by LH at a step before the adenylate cyclase; (ii) phospholipids play an important role in cAMP-stimulated testosterone synthesis.
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PMID:Effect of phorbol ester and phospholipase C on LH-stimulated steroidogenesis in purified rat Leydig cells. 299 25


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