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