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)

Batrachotoxin (BTX), veratridine and monensin induced a time- and dose-dependent increase of [3H]-inositol monophosphate (3H-IP1) accumulation in the presence of lithium in prelabeled neurohybrid NCB-20 cells. A decrease of NaCl concentration to less than 30 mM markedly increased basal 3H-IP1 accumulation; however, the percentage of stimulation induced by these three agents remained unchanged even in the complete absence of sodium. The stimulation of phosphoinositide hydrolysis induced by these agents was detected in the absence of lithium but was largely prevented in the calcium-free medium. Tetradotoxin (TTX) blocked effects of BTX and veratridine (IC50 approximately 20nM), but not that stimulated by monensin. Thus, calcium-dependent activation of phospholipase C by these agents did not involve the entry of sodium or lithium. BTX and monensin also induced greater than additive effects on carbachol-induced 3H-IP1 accumulation. These effects were also TTX-sensitive and involved an increase in the Vmax and a decrease in the EC50 for carbachol. Veratridine provoked strikingly different effects on carbachol-dependent phosphoinositide turnover, depending on the passage number of the cells.
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PMID:Regulation by batrachotoxin, veratridine, and monensin of basal and carbachol-induced phosphoinositide hydrolysis in neurohybrid NCB-20 cells. 216 25

The sodium channel activators veratridine and batrachotoxin, the sodium ionophore gramicidin, and the calcium ionophore ionomycin stimulated phosphoinositide breakdown, as indicated by the increased accumulation of [3H]inositol monophosphate in embryonic chick heart cells. The levels of [3H]inositol trisphosphate and [3H]inositol bisphosphate were also increased by veratridine, indicating that there was increased hydrolysis of phosphatidylinositol bisphosphate by phospholipase C. The response to veratridine required both extracellular sodium and calcium, suggesting that calcium entry via Na/Ca exchange might activate phospholipase C. Fluorescence measurements with fura-2 confirmed that the sodium agents greatly increased the cytoplasmic calcium concentration. Veratridine (100 microM) increased cytoplasmic calcium from 94 +/- 4 nM to 862 +/- 103 nM, giving a maximal calcium increase in about 2 min. Batrachotoxin (1 microM) induced an even greater increase in calcium but required a longer time. Gramicidin also induced a large increase in cytoplasmic calcium which was maximal within 0.5 min. To directly test the calcium dependency of phospholipase C, we permeabilized the chick heart cells with saponin and monitored the production of inositol phosphates at different calcium concentrations. Raising the calcium concentration from 3 to 1000 nM increased the accumulation of [3H]inositol phosphates by nearly 4-fold with a half-maximal effect at about 200 nM calcium. The guanine nucleotide guanosine-5'-O-(3-thio)triphosphate (GTP gamma S) also stimulated accumulation of the InsPs and the response to (GTP gamma S) was potentiated by increasing the calcium concentration. The data suggest that the effect of the sodium agents on phosphoinositide hydrolysis results from an elevation of intracellular calcium which increases GTP-dependent phospholipase C activity. Thus, drugs or other conditions that elevate cytoplasmic calcium in heart cells may increase the hydrolysis of membrane phosphoinositides.
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PMID:Elevation of cytoplasmic calcium concentration stimulates hydrolysis of phosphatidylinositol bisphosphate in chick heart cells: effect of sodium channel activators. 245 Nov 16

Chromaffin cells purified from bovine adrenal medulla and maintained in primary culture were used to study the effects of hyperosmolarity on the nicotine- and high potassium-induced secretory response. A similar study was also performed on cells permeabilized with digitonin and with alpha-toxin from Staphylococcus aureus. Hyperosmolarity does not affect the spontaneous release of catecholamines from either intact cells or permeabilized cells. The nicotine-induced secretion and high potassium-induced secretion from intact cells are inhibited by hypertonic solutions; a 100% inhibition of net release was observed at 660 mOsm (sucrose as osmotic agent). Veratridine- and the cation ionophore X537-A-induced release were both depressed under hyperosmotic conditions. Hyperosmolarity was shown to have reversible effects on the secretory response of intact cells. Finally, hyperosmolarity has intracellular effects on catecholamine release evoked by calcium from both detergent- and alpha-toxin-permeabilized cells. Our data show that hyperosmolarity has multiple effects on the cell membrane and the protein constituents associated with it, but has also a significant effect on intracellular reactions concerned with exocytosis.
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PMID:Influence of hypertonic solutions on catecholamine release from intact and permeabilized cultured chromaffin cells. 379 Jun 19

We studied the phosphorylation of tyrosine hydroxylase in the superior cervical ganglion of the rat. Ganglia were preincubated with [32P]Pi and were then incubated in non-radioactive medium containing a variety of agents that are known to activate tyrosine hydroxylase in this tissue. Tyrosine hydroxylase was isolated from homogenates of the ganglia by immunoprecipitation followed by polyacrylamide gel electrophoresis. 32P-labelled tyrosine hydroxylase was visualized by radioautography, and the incorporation of 32P into the enzyme was quantitated by densitometry of the autoradiograms. Veratridine produced a concentration-dependent increase in the incorporation of 32P into tyrosine hydroxylase, with 50 microM veratridine producing a 5-fold increase in 32P incorporation. The nicotinic agonist, dimethylphenylpiperazinium (100 microM), caused a 7-fold increase in the phosphorylation of tyrosine hydroxylase. The effect of dimethylphenylpiperazinium was maximal within 1 min and decreased upon continued exposure of the ganglia to this agent. The actions of dimethylphenylpiperazinium and of veratridine were dependent on extracellular Ca2+. Muscarine, 8-Br-cAMP, forskolin, vasoactive intestinal peptide, isoproterenol, deoxycholate and phospholipase C also stimulated the incorporation of 32P into tyrosine hydroxylase. These data support the hypothesis that phosphorylation plays a role in activation of tyrosine hydroxylase produced by all of these agents.
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PMID:Phosphorylation of tyrosine hydroxylase in the superior cervical ganglion. 614 69

At least six topologically separated neurotoxin receptor sites have been identified on sodium channels that reveal strong allosteric interactions among them. We have studied the allosteric modulation induced by veratridine, binding to receptor site 2, and brevetoxin PbTx-1, occupying receptor site 5, on the binding of alpha-scorpion toxins at receptor site 3, on three different neuronal sodium channels: rat brain, locust, and cockroach synaptosomes. We used 125I-AaH II, the most active alpha-scorpion toxin on vertebrates, and 125I-Lqh alpha IT, shown to have high activity on insects, as specific probes for receptor site 3 in rat brain and insect sodium channels. Our results reveal that brevetoxin PbTx-1 generates three types of effects at receptor site 3:1) negative allosteric modulation in rat brain sodium channels, 2) positive modulation in locust sodium channels, and 3) no effect on cockroach sodium channel. However, PbTx-1 activates sodium channels in cockroach axon similarly to its activity in other preparation. Veratridine positively modulates both rat brain and locust sodium channels but had no effect on alpha-toxin binding in cockroach. The dramatic differences in allosteric modulations in each sodium channel subtype suggest structural differences in receptor sites for PbTx-1 and/or at the coupling regions with alpha-scorpion toxin receptor sites in the different sodium channels, which can be detected by combined application of specific channel modifiers and may elucidate the dynamic gating activity and the mechanism of allosteric interactions among various neurotoxin receptors.
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PMID:Alpha-scorpion toxins binding on rat brain and insect sodium channels reveal divergent allosteric modulations by brevetoxin and veratridine. 779 99

Voltage-gated sodium channels serve as a target for many neurotoxins that bind to several distinct, allosterically interacting receptor sites. We examined the effect of membrane potentials (incited by increasing external K+ concentrations) on the binding modulation by veratridine, brevetoxin, and tetrodotoxin of the scorpion alpha-toxin AaH II to receptor site 3 on sodium channels of rat brain synaptosomes. Depolarization is shown to differentially modulate neurotoxin effects on AaH II binding: Veratridine increase is potentiated, brevetoxin's inhibitory effect is reduced, and tetrodotoxin enhancement is evident mainly at resting membrane potential (5 mM K+). Both tetrodotoxin and veratridine apparently reverse the inhibition of AaH II binding by brevetoxin at resting membrane potential, but only veratridine is able to partially restore AaH II binding at 0 mV (135 mM K+). Thus, the allosteric interactions are grouped into two categories, depending on the membrane potential. Under depolarized conditions, the cooperative effects among veratridine and brevetoxin on AaH II binding fit the previously described two-state conformational model. At resting membrane potential, additional interactions are revealed, which may be explained by assuming that toxin binding induces conformational changes on the channel structure, in addition to being state-dependent. Our results provide a new insight into neurotoxin action and the complex dynamic changes underlying allosteric coupling of neurotoxin receptor sites, which may be related to channel gating.
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PMID:Depolarization differentially affects allosteric modulation by neurotoxins of scorpion alpha-toxin binding on voltage-gated sodium channels. 948 44

The function of the prion protein is unknown despite suggestions it binds copper. Radioactive copper (Cu(67)) was used to demonstrate that histidine-dependent uptake of copper by cerebellar cells in culture is related to the level of PrP(c) expression. Copper is released by neurones at the synapse. Veratridine-induced release from synapses was proportional to the level of PrP(c) expression. Veratridine-induced release can be abolished only from PrP(c) expressing cells by pretreatment with phosphatidyl-specific phospholipase C, an enzyme that cleaves PrP(c) from the cell surface. These results suggest that PrP(c) aids cellular copper uptake and may have a function at the synapse related to release of copper during transmission.
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PMID:Prion protein expression aids cellular uptake and veratridine-induced release of copper. 1056