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)

Carbachol, a muscarinic receptor agonist and the sodium channel-activating agents, scorpion venom, veratridine, batrachotoxin and aconitine, were shown to stimulate the formation of [3H]inositol phosphates in [3H]inositol-labelled miniprisms, obtained from the cerebral cortex of the mouse. The inositol response to the Na+ channel-activating agents was inhibited by the sodium channel blocker tetrodotoxin (TTX), while the response induced by carbachol was partially resistant to TTX. The response to scorpion venom and the TTX-insensitive portion of the response to carbachol was additive, indicating different mechanisms. The presence of high potassium (K+) induced hydrolysis of inositide in a TTX-insensitive manner and was not additive with that resulting from sodium channel activators, thus indicating a common mechanism. The addition of large concentrations of magnesium to block the release of acetylcholine, did not inhibit the inositol response to high K+ or to veratridine. Calcium channel blockers such as nickel or cobalt, or the dihydropyridine calcium (Ca2+) channel activator BAY K 8644 and the calcium channel blocker nifedipine, nimodipine or PN-200 110 had little effect. Monensin, a sodium ionophore, stimulated the turnover of phosphatidylinositol at non-depolarizing concentrations and the omission of Na+ ions inhibited the response to sodium channel agents and to high K+. Thus, membrane potential and gradients of K+, Na+ and Ca2+ are all important factors determining the final effect on the turnover of phosphatidylinositol. The data are consistent with a model in which all these factors impinge on the Na+/Ca2+ exchanger regulating internal Ca2+ that, in turn, activates phospholipase C.
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PMID:Phosphoinositide hydrolysis induced by depolarization and sodium channel activation in mouse cerebrocortical slices. 255 Aug 41

Activation of alpha 1-adrenergic receptors increases [Ca+2]i and phosphatidylinositol phosphodiesterase (phospholipase C) activity in the pinealocyte. In this report the receptor involved in the stimulation of phospholipase C activity was further characterized, and the role of Ca2+ in this effect was investigated in some detail. Phospholipase C activity was estimated by measuring the production of [3H]inositol phosphates by [3H]inositol-labelled dispersed pinealocytes in suspension culture. Norepinephrine stimulated [3H]inositol monophosphate production severalfold; this was blocked by alpha 1-adrenergic antagonists, including prazosin, WB 4101, and phenoxybenzamine, but by neither an alpha 2- nor a beta-adrenergic antagonist, confirming that an alpha 1-adrenoceptor is involved in the regulation of phosphatidylinositol hydrolysis. Treatment with the Ca2+ chelator, EGTA, or with inorganic Ca2+ blockers, including Co2+, Mn2+, and La3+, reduced the norepinephrine-stimulated response, suggesting that the alpha 1-adrenergic stimulation of phospholipase C activity is Ca2+ dependent. However, phospholipase C activity was not increased by elevating intracellular Ca2+ with either the Ca2+ ionophore A23187 or with depolarizing concentrations of K+. These results indicate that although Ca2+ is necessary for alpha 1-adrenergic stimulation of phospholipase C activity, an increase in [Ca2+]i alone is not sufficient to stimulate the activity of this enzyme, and that effects which A23187 and depolarizing concentrations of K+ have on pineal function probably do not involve stimulation of phospholipase C activity.
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PMID:Permissive role of calcium in alpha 1-adrenergic stimulation of pineal phosphatidylinositol phosphodiesterase (phospholipase C) activity. 290 66

The coordination sphere of both the structural and catalytic zinc ions of Bacillus cereus phospholipase C has been probed by substitution of cobalt(II) for zinc and investigation of the resultant derivatives by a variety of spectroscopic techniques. The electronic absorption, circular dichroic, magnetic circular dichroic, and electron paramagnetic resonance spectra were found to be strikingly similar when cobalt(II) was substituted into either site and are consistent with a distorted octahedral environment for the metal ion in both sites. Octahedral coordination appears comparatively rare in zinc metalloenzymes but has been suggested for glyoxalase I [Sellin, S., Eriksson, L. E. G., Aronsson, A.-C., & Mannervik, B. (1983) J. Biol. Chem. 258, 2091-2093; Garcia-Iniguez, L., Powers, L., Chance, B., Sellin, S., Mannervik, B., & Mildvan, A. S. (1984) Biochemistry 23, 685-689], transcarboxylase [Fung, C.-H., Mildvan, A. S., & Leigh, J. S. (1974) Biochemistry 13, 1160-1169], and the regulatory binding site of Aeromonas aminopeptidase [Prescott, J. M., Wagner, F. W., Holmquist, B., & Vallee, B. L. (1985) Biochemistry 24, 5350-5356]. Phospholipase C is so far unique in having two such sites.
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PMID:A spectral study of cobalt(II)-substituted Bacillus cereus phospholipase C. 301 84

Phospholipid metabolites have previously been implicated in receptor-mediated stimulation of protein hormone secretion. As the factors which regulate the release of choriomammotrophin remain to be elucidated, we investigated the potential involvement of phospholipase C-induced phospholipid metabolism in the release of this placental hormone. Phospholipase C (PLC) caused a dose-dependent release of choriomammotrophin from ovine placenta, incubated in vitro. At a concentration of 0.2 units/ml (0.25 microgram protein/ml), PLC caused the release of choriomammotrophin from placental tissue to approximately double that observed in control incubations (7.08 +/- 0.4 micrograms/50 mg/h and 3.26 +/- 0.3 micrograms/50 mg/h, respectively). PLC treatment did not significantly alter plasma membrane permeability, as indicated by the release of lactate dehydrogenase and protein. PLC-stimulated release of oCM was completely abolished by incubation in calcium-free medium or by preincubation with the inorganic calcium-channel blocking agents cobalt chloride (4 mM) and lanthanum chloride (1 mM). The effects of PLC treatment on ovine choriomammotrophin (oCM) release were also inhibited by preincubation of placental tissue with inhibitors of arachidonic acid metabolism: ibuprofen (10(-5) M), naproxen (10(-4) M) or nordihydroguaiaretic acid (NDGA) 5 X 10(-6) M). These results suggest that the effects of PLC on the release of choriomammotrophin are mediated via metabolites of arachidonic acid.
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PMID:Stimulation of ovine choriomammotrophin release, in vitro, by phospholipase C. 309 78

Auranofin (AF) is an orally active chrysotherapeutic agent used for the treatment of rheumatoid arthritis, a self-perpetuating inflammatory disease. Because of reports suggesting that AF and other gold complexes can, under certain circumstances, exacerbate rheumatoid inflammatory lesions in humans and adjuvant arthritic rats and that phospholipase C (PLC) and phospholipase A2 activities are increased in rheumatoid patients, the effects of AF and a related gold complex on in situ mammalian and purified Bacillus cereus PLC were examined. Results of our studies show that 1) AF and triethylphosphine gold chloride (TEPG), an AF analog, stimulated PLC activity in the sonicate of RAW 264.7 macrophages; 2) AF and TEPG stimulated B. cereus PLC activity in a concentration-dependent manner, but the pattern of stimulation and concentrations of drugs required to stimulate the purified enzyme differ from those seen with the macrophage PLC; 3) metals (cobalt and zinc) and sulfhydryl reagents (N-ethylmaleimide, iodoacetic acid, and glutathione), tested at the same concentrations of AF that enhanced PLC activity, had no effect on the enzyme. These data suggest that stimulation of PLC may be a generic phenomenon since two divergent PLCs are affected by gold complexes. Additionally, these studies may provide one potential explanation for rheumatoid lesion flares seen in patients and animals on chrysotherapy.
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PMID:Effect of auranofin and other gold complexes on the activity of phospholipase C. 311 79

Maitotoxin (3 ng/mol) induced a massive uptake of 45Ca2+ into BC3H1 cells. This effect exhibits a lag phase of 3 min. Inositol diphosphate formation occurred concomittantly with the 45Ca2+ uptake but inositol monophosphate formation was found only after a 5-min delay following toxin addition. Maitotoxin-induced 45Ca2+ influxes could not be blocked by either 1 microM verapamil, 1 microM nifedipine or 1 mM La3+ but was blocked by Zn2+ (IC50 = 41 microM). In addition to inositol phosphate formation and 45Ca2+ uptake, maitotoxin stimulated a large uptake of Na+ and a great loss of K+ in BC3H1 cells. In the absence of Ca2+ (1 mM EGTA) none of the four maitotoxin effects could be detected. After restoration of Ca2+, the maitotoxin effects reappeared even when the toxin itself was no longer present. The divalent cation, Co2+ (1 mM), inhibited ion movements induced by maitotoxin and also digitonin (8.1 microM). The toxin action showed a very pronounced pH dependence. At low pH, maitotoxin was inactive. The dose-response curves for H+ ion inhibition of maitotoxin-induced Ca2+ uptake showed a shift to the right when determined in the absence of HCO3- and HCO3-/Cl- ions. It was concluded that the primary action of maitotoxin in BC3H1 cells was a pore-forming or channel-forming activity of a non-classical type. Some properties of maitotoxin resemble those of alpha-latrotoxin, others those of pore-forming agents such as melittin or alpha-toxin of Staphylococcus aureus.
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PMID:New insights into maitotoxin action. 339 Nov 76

An enzyme hydrolysing the synthetic substrate p-nitrophenylphosphorylcholine was highly active in the epididymal caput and very low or absent in other parts of the bovine reproductive organs. This enzyme was also found in the secretory fluid obtained from the epididymal caput but much lower activities were encountered in cauda epididymis and seminal plasma. The enzyme displayed an optimum at pH 6.5, an Mr of about 66000, a pI value of 5.0 and was suppressed by chelating agents and reactivated by Co2+ and Zn2+. After partial purification the enzyme also showed hydrolysis of p-nitrophenyl phenylphosphonate, bis-p-nitrophenyl phosphate and hexadecanoyl-p-nitrophenylphosphorylcholine with slightly different pH optima and modifier characteristics. It is concluded that this secretory enzyme is distinct from the membrane-bound phospholipase C and may play a role in processing of the spermatozoan phospholipids during the epididymal maturation.
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PMID:A secretory phospholipase C-like enzyme in the bovine epididymal caput. 372 Sep 58

Three different phospholipases C--the so-called phospholipase C which hydrolyses phosphatidylcholine (Pch-PLC), sphingomyelinase (SM-PLC) and phosphatidylinositol hydrolysing phospholipase C (PI-PLC)--were separated from the culture filtrate of Bacillus cereus using column chromatography on DEAE-sephadex A-50. The pI values were estimated to be 5.0 +/- 0.3 for PI-PLC and 5.3 +/- 0.2 for SM-PLC. The effect of some bivalent cations was studied. Metal ions had no effect on the activity of PI-PLC, whereas Mg2+ and Co2+ in concentrations from 1 to 5 mM highly activated SM-PLC. Mg2+ failed to activate PCh-PLC, and Co2+ even inhibited it. EDTA of o-phenantroline had a rather inhibitory effect on Pch-PLC, but they almost did not affect SM-PLC.
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PMID:[Properties of the phospholipases C from Bacillus cereus]. 392 53

Purified, electrophoretically homogeneous phospholipase C (PLC) preparations can be separated into two peaks by isoelectric focusing in sucrose gradients. The main peak has an isoelectric pH of 6.6-6.8 and contains two Zn2+ per molecule. The more acid peak (isoelectric pH about 6.2) contains about one Zn2+ per molecule and has a markedly reduced specific activity which can be raised by adding Zn2+. The purified enzyme has a low sphingomyelinase activity which coincides completely with the lecithinase activity in fractions from isoelectric focusing. The sphingomyelinase activity was greatly enhanced by substitution of Co2+ for Zn2+ but remained essentially unaltered when the levels of Ca2+ and Mg2+ were changed. These findings provide evidence that the sphingomyelinase activity is a true endogenous activity of PLC and not caused by contaminating sphingomyelinase.
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PMID:Phospholipase C from Bacillus cereus has sphingomyelinase activity. 629 Nov 30

The adenylate cyclase and Na+ -K+ ATPase activities decreased on storage at 4 degrees C as well as on freezing and thawing of the rat heart sarcolemma. Treatment of the sarcolemmal fraction with phospholipase C and trypsin also depressed the adenylate cyclase and Na+ -K+ ATPase activities; the Na+ -K+ ATPase was more sensitive to these treatments than the adenylate cyclase. When the sarcolemmal enzyme activities were determined in the presence of different concentrations of some cations the adenylate cyclase activity was enhanced and the Na+ -K+ ATPase activity was depressed by monovalent cations (Na+, K+, Rb+, Cs+, Li+, and NH+4). Divalent cations such as Sr2+, Ba2+, Co2+, and Mn2+ had biphasic or no effects on the adenylate cyclase activity but inhibited the Na+ -K+ ATPase activity. Although Ca2+, Ni2+, Cd2+, Cu2+, Hg2+, and Zn2+ depressed both Na+ -K+ ATPase and adenylate cyclase activities, the degree of inhibition of these enzymes was different. These results reveal the role of membrane integrity for full expression of the adenylate cyclase and Na+ -K+ ATPase activities, whereas both monovalent and divalent cations appear to regulate sarcolemma-bound enzyme activities.
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PMID:Role of membrane integrity and cation interaction for heart sarcolemmal adenylate cyclase and Na+-K+ ATPase. 630 75


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