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

Angiotensin II stimulates sequential phospholipase C-mediated hydrolysis of initially the polyphosphoinositides and subsequently phosphatidylinositol (PI) in cultured rat aortic smooth muscle cells resulting in biphasic, sustained formation of diacylglycerol (DG). The mechanisms underlying this delayed induction of sustained DG accumulation are unknown but may be related to cellular events including processing of the angiotensin II receptor-ligand complex. In the present study, we characterized the kinetics of angiotensin II receptor sequestration and studied the effects of interventions which interfere with receptor processing on the pattern of angiotensin II-induced DG formation and phosphoinositide hydrolysis. Conversion of the angiotensin II receptor to an acid-resistant form was temperature-dependent, with half-times of 1.5 min at 37 degrees C and 7 min at 19 degrees C. Reducing the temperature to 25 or 19 degrees C caused a marked temporal separation between the two phases of DG accumulation. There was a close temporal correlation between the effect of temperature on receptor sequestration and on sustained DG accumulation. Furthermore, phenylarsine oxide (5 min, 10 microM), which inhibited angiotensin II receptor internalization, also selectively inhibited the sustained phase of DG accumulation (81 +/- 6% inhibition). Monensin and chloroquine, which interfere with receptor processing through the lysosomal-degradative pathway, had no effect on angiotensin II-induced DG formation in these cells, suggesting that the processing event important to hormonally induced sustained DG accumulation occurs early in the internalization pathway, probably at the level of the plasma membrane. Moreover, the acid-resistant state of the angiotensin II receptor-ligand complex retained its ability to signal, since removal of the surface signal by competitive antagonism with Sar1-Ile8-angiotensin II or acid-wash only slowly reversed accumulation of DG and depression of total cell calcium. These experiments support our previous observation that the initial and sustained phases of angiotensin II-induced diacylglycerol formation in vascular smooth muscle are differentially controlled and suggest that an early event in the cellular processing of the angiotensin II-receptor complex is essential to maintenance of DG accumulation.
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PMID:Correlation of receptor sequestration with sustained diacylglycerol accumulation in angiotensin II-stimulated cultured vascular smooth muscle cells. 282 94

We have investigated the abnormal proliferation and morphology of fibroblasts from patients with Tangier disease (TD), a high density lipoprotein (HDL) deficiency syndrome that is characterized by impairment of HDL3-mediated lipid efflux and Gi-protein-mediated signaling via phosphatidylinositol-specific phospholipase C (PI-PLC) and phospholipase D (PLD). TD fibroblasts displayed a 30% to 50% reduced in vitro growth rate and a 1.6-fold increased cell surface area. The response to different mitogens was diminished, and asynchronously growing TD fibroblasts showed 4.4+/-0.3% S-phase and 19.1+/-0.5% G2/M-phase cells compared with 9.7+/-0.6% and 7.8+/-0.5%, respectively, in controls. Monensin, but not brefeldin A, induced an S- and G2/M-phase distribution in control cells similar to that found in TD fibroblasts. This effect of monensin was accompanied by an increase of ceramide levels in controls, whereas TD fibroblasts already had a 2.5-fold increased basal ceramide concentration. Incubation of control cells with C2 ceramide and threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) mimicked the effect of monensin on the cell cycle. The inhibition of neither Gi protein function by pertussis toxin nor PLD by butanol resulted in a G2/M-phase arrest. Propranolol, known to increase phosphatidic acid levels, was ineffective in reversing the G2/M-phase arrest in TD fibroblasts. In addition, cDNA sequences and mRNA expression of the participants of PI-PLC or PLD signaling, ie, G-protein subunits alphai1, alphai2, and alphai3; phosphatidylinositol transfer proteins-alpha and -beta; and ADP ribosylation factors 1 and 3 were found to be normal. Thus, growth and cell cycle abnormalities in TD fibroblasts are likely to be related to impaired Golgi function and sphingolipid signaling rather than inoperative G-protein signal transduction. Because PDMP was also found to decrease HDL3-mediated lipid efflux in control but not TD fibroblasts, similar pathways seem to be involved in the disturbances of lipid transport and growth retardation.
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PMID:Growth and cell cycle abnormalities of fibroblasts from Tangier disease patients. 988 63

Matrix vesicles are extracellular organelles involved in mineral formation that are regulated by 1alpha,25(OH)(2)D(3). Prior studies have shown that protein kinase C (PKC) activity is involved in mediating the effects of 1alpha,25(OH)(2)D(3) in both matrix vesicles and plasma membranes. Here, we examined the regulation of matrix vesicle PKC by 1alpha,25(OH)(2)D(3) during biogenesis and after deposition in the matrix. When growth zone costochondral chondrocytes were treated for 9 min with 1alpha,25(OH)(2)D(3), PKCzeta in matrix vesicles was inhibited, while PKCalpha in plasma membranes was increased. In contrast, after treatment for 12 or 24 h, PKCzeta in matrix vesicles was increased, while PKCalpha in plasma membranes was unchanged. The effect of 1alpha,25(OH)(2)D(3) was stereospecific and metabolite-specific. Monensin blocked the increase in matrix vesicle PKC after 24 h, suggesting the secosteroid-regulated packaging of PKC. In addition, the 1alpha,25(OH)(2)D(3) membrane vitamin D receptor (1,25-mVDR) was involved, since a specific antibody blocked the 1alpha,25(OH)(2)D(3)-dependent changes in PKC after both long and short treatment times. In contrast, antibodies to annexin II had no effect, and there was no evidence for the presence of the nuclear VDR on Western blots. To investigate the signaling pathways involved in regulating matrix vesicle PKC activity after biosynthesis, matrix vesicles were isolated and then treated for 9 min with 1alpha,25(OH)(2)D(3) in the presence and absence of specific inhibitors. Inhibition of phosphatidylinositol-phospholipase C, phospholipase D, or G(i)/G(s) had no effect. However, inhibition of G(q) blocked the effect of 1alpha,25(OH)(2)D(3). The rapid effect of 1alpha,25(OH)(2)D(3) also involved the 1,25-mVDR. Moreover, arachidonic acid was found to stimulate PKC when added directly to isolated matrix vesicles. These results indicate that matrix vesicle PKC is regulated by 1alpha,25(OH)(2)D(3) at three levels: 1) during matrix vesicle biogenesis; 2) through direct action on the membrane; and 3) through production of other factors such as arachidonic acid.
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PMID:1alpha,25(OH)2D3 regulates chondrocyte matrix vesicle protein kinase C (PKC) directly via G-protein-dependent mechanisms and indirectly via incorporation of PKC during matrix vesicle biogenesis. 1180

In this study, we examined the inhibitory mechanism of monensin on high K+-induced contraction in guinea-pig urinary bladder. The relaxant effect of monensin (0.001 - 10 microM) was more potent than those of NaCN (100 microM - 1 mM) and forskolin (3 - 10 microM). Monensin (0.1 microM), NaCN (300 microM), or forskolin (10 microM) inhibited high K+-induced contraction without decreasing [Ca2+]i level. Monensin and NaCN remarkably decreased creatine phosphate and ATP contents. Monensin and NaCN inhibited high K+-induced increases in flavoprotein fluorescence, which is involved in mitochondrial respiration. Forskolin increased cAMP content but monensin did not. Monensin increased Na+ content at 10 microM but not at 0.1 microM that induced maximum relaxation. In the alpha-toxin-permeabilized muscle, forskolin significantly inhibited the Ca2+-induced contraction, but monensin did not affect it. These results suggest that the relaxation mechanism of monensin in smooth muscle of urinary bladder may be an inhibition of oxidative metabolism.
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PMID:Inhibitory mechanism of monensin on high K+-induced contraction in guniea-pig urinary bladder. 1647 6