Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IMR-32 and SK-N-MC cells were found to contain [3H]quinuclidinyl benzilate specific binding sites inhibited by pirenzepine in a manner suggesting the presence of both M1-type and M2-type muscarinic receptor recognition sites. Neither cell had detectable [3H]8-OH-DPAT binding sites. Carbachol stimulated the rate of inositol phospholipid breakdown in IMR-32 and SK-N-MC human neuroblastoma cells with an EC50 value of about 50 microM in both cases. Pirenzepine inhibited the carbachol (100 microM)-stimulated inositol phospholipid breakdown in both cells with Hill slopes of unity and IC50 values of 15 nM (IMR-32) and 12 nM (SK-N-MC). The 5-HT1A receptor agonist 8-OH-DPAT competitively inhibited carbachol-stimulated inositol phospholipid breakdown with pA2 values of 5.78 (IMR-32) and 5.61 (SK-N-MC). These values are consistent with the inhibitory potency of 8-OH-DPAT towards [3H]quinuclidinyl benzilate binding in these cells. The 5-HT agonists 5-MeODMT and buspirone at micromolar concentrations inhibited carbachol-stimulated breakdown in IMR-32 cells. The inhibition by 8-OH-DPAT and 5-MeODMT was not affected by preincubation with (-)alprenolol. 5-HT (10-100 microM) was without effect on either basal or carbachol-stimulated breakdown. It is concluded that IMR-32 and SK-N-MC neuroblastoma cells express muscarinic M1-type but not serotoninergic receptors coupled to phosphoinositide-specific phospholipase C. 8-OH-DPAT acts as a weak antagonist at these muscarinic receptors.
...
PMID:Antagonism by 8-hydroxy-2(di-n-propylamino)tetraline and other serotonin agonists of muscarinic M1-type receptors coupled to inositol phospholipid breakdown in human IMR-32 and SK-N-MC neuroblastoma cells. 182 86

The ability of angiotensin peptides to stimulate prostaglandin release and raise intracellular calcium levels by activating a phosphoinositide-specific phospholipase C was assessed in three human astrocytoma cell lines (CRTG3, STTG1, and WITG2). The addition of angiotensin II to CRTG3 cells resulted in a dose-dependent release of prostaglandin E2 and prostacyclin, the production of inositol 1,4,5-trisphosphate, and the mobilization of intracellular calcium. Angiotensin-(1-7), previously considered to be an inactive metabolite of angiotensin II, was as potent as angiotensin II for prostaglandin release but did not activate phospholipase C or mobilize intracellular calcium. In contrast, angiotensin-(2-8) caused only a slight increase in prostaglandin release, even though it was as effective as angiotensin II in augmenting inositol 1,4,5-trisphosphate production and calcium mobilization. Moreover, neither the release of prostaglandins in response to angiotensin II or angiotensin-(1-7) nor the mobilization of intracellular calcium in response to angiotensin II required extracellular calcium. Angiotensin II and angiotensin-(1-7) caused the release of prostaglandins from all three human astrocytoma cell lines, but changes in the level of intracellular calcium in response to angiotensin II only occurred in CRTG3 cells. Although previous studies have provided evidence for angiotensin receptor subtypes on the basis of selectivity of antagonists or signal transduction mechanisms, these data suggest that human astrocytes contain multiple angiotensin receptor subtypes on the basis of their response to different angiotensin heptapeptides--angiotensin-(1-7) and angiotensin-(2-8).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Human astrocytes contain two distinct angiotensin receptor subtypes. 186 Jul 9

Since phosphoinositide-specific phospholipase C (PLC) is one of the key molecules in signal transduction, the authors assessed its involvement in Alzheimer's disease (AD). Immunostaining of a specific antibody against the PLC isozyme, PLC-delta, demonstrated that this enzyme was abnormally accumulated in neurofibrillary tangles (NFT), the neurites surrounding senile plaque (SP) cores, and neuropil threads in AD brains. Western blot analysis confirmed that PLC-delta was concentrated in the paired helical filament (PHF)-rich fraction of AD brains. Antibodies to other PLC isozymes did not produce positive immunostaining of these pathologic structures. Moreover, diffuse and amorphous deposits of PLC-delta were found to precede the accumulation of fibrillary deposits. These results suggest that PLC-delta accumulation is a crucial event that ultimately may contribute to the formation of PHF.
...
PMID:Aberrant accumulation of phospholipase C-delta in Alzheimer brains. 192 98

We showed previously that glomerular mesangial cells displayed increased fibronectin, laminin, and type IV collagen synthesis and mRNA levels when grown in medium containing 30 mM glucose compared with those cells grown in 10 mM glucose [S. H. Ayo, R. A. Radnik, W. F. Glass II, J. A. Garoni, E. R. Rampt, D. R. Appling, and J. I. Kreisberg. Am. J. Physiol. 260 (Renal Fluid Electrolyte Physiol. 29): F185-F191, 1990]. However, total protein synthesis and actin mRNA were unchanged. In this report, we show that an increase in medium glucose concentration resulted in an increase in diacylglycerol (DAG) mass and transiently increased protein kinase C (PKC) activity as assessed by the translocation of PKC from the soluble to the particulate fraction. Effects of increased glucose on DAG were evident at 30 min and were maintained through 1 wk of growth in medium containing 30 mM glucose. Although total PKC activity (i.e., soluble plus particulate fractions) did not change with high-glucose treatment, the percent activity associated with the particulate fraction (i.e., activated PKC) increased significantly after 60 min in RPMI 1640 medium with 30 mM glucose. The distribution of PKC returned to control values by 24 h. High glucose did not stimulate phosphoinositide hydrolysis, as evidenced by the absence of an increase in the water-soluble inositol phosphates, indicating that DAG was not generated through the action of a phosphoinositide-specific phospholipase C. Cells treated with the cell-permeable DAG analogue 1-oleoyl-2-acetyl glycerol to activate PKC displayed approximately two-fold increases of fibronectin, laminin, and type IV collagen mRNA levels after normalization against actin.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:High glucose increases diacylglycerol mass and activates protein kinase C in mesangial cell cultures. 192 72

Most of the phosphoinositide-specific phospholipase C activity in human amnion at term was found to be attributable to a single isoform (Mr 85,000). Phospholipase C purified from amnion catalyzed the calcium-dependent hydrolysis of both phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate. The high phospholipase C activity of amnion cells isolated at 38-41 weeks of gestation declined greater than 80% during the initial 2-5 days of culture to values characteristic of amnion tissue in early gestation. Activities of phospholipase A2 and phosphatidylinositol synthase remained essentially unaltered during this period of culture. Loss of phospholipase C activity was apparently due neither to the appearance of an inhibitor nor to the loss of an activator and most likely reflected a decrease in the amount of enzyme in amnion cells. Basal production of prostaglandin E2 (PGE2) by amnion cells also declined greatly during the period of loss of phospholipase C activity. Involvement of phospholipase C in the regulation of amnion prostaglandin production was also supported by the finding that the phospholipase C inhibitor, U-73122, potently inhibited amnion cell PGE2 production. In contrast, vasopressin, which appears to stimulate prostaglandin production in amnion cells by a phospholipase C-dependent mechanism, was equipotent in stimulating PGE2 production by amnion cells on Day 2 and Day 5 of culture, even though phospholipase C activity had declined by more than 75%. Furthermore, epidermal growth factor stimulation of PGE2 production by amnion cells appeared to be largely attributable to an increase in prostaglandin H synthase activity and did not involve an increase in phospholipase C activity.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Characterization of the major phosphoinositide-specific phospholipase C of human amnion. 196 96

1. The mechanism of gastroprotective action of an antiulcer drug, sucralfate, was investigated. Studies in vivo were conducted with groups of rats with and without indomethacin pretreatment, and the animals received sucralfate followed by ethanol. In the in vitro system, gastric mucosa was cultured in the presence of sucralfate with and without indomethacin. 2. The in vivo experiments revealed that ethanol caused extensive gastric lesions which were significantly reduced following sucralfate pretreatment. Furthermore, sucralfate was also capable of preventing the detrimental effect of indomethacin on gastric mucus gel dimension and its mucin content. 3. The data with gastric mucosal culture showed that the sucralfate elicited increase in mucin was accompanied by the enhanced turnover of mucosal phosphoinositides. 4. Regardless of the inclusion of indomethacin, sucralfate evoked 23% reduction in phosphatidylinositol, 24% increase in inositol-1-phosphate and 3.4-fold increase in inositol-1,4,5-trisphosphate, thus indicating the activation of phosphoinositide-specific phospholipase C. 5. The results demonstrate that the gastric mucosal protective action of sucralfate is not mediated by endogenous prostaglandins, but appears to involve the metabolism of phosphoinositide-derived messenger molecules.
...
PMID:Gastric mucosal protection by sucralfate involves phosphoinositides participation. 196 55

ADP-ribosyltransferase from Clostridium botulinum type C strain was found to induce an increase of inositol phosphates (IPs) formation in murine thymocytes membranes. Incubation of electropermeabilized murine thymocytes with the enzyme also caused an increase of IPs formation in the cells. This increase of IPs formation in the enzyme-treated membranes and electropermeabilized cells was dependent on the amount of both NAD and the enzyme, suggesting that the stimulation of phosphoinositide-specific phospholipase C (PLC) was related to ADP-ribosylation of membrane proteins by the enzyme. On the other hand, in calf and murine thymocytes two proteins with the same molecular weight of 21,000 were found to be ADP-ribosylated by the botulinum ADP-ribosyltransferase. A minor ADP-ribosylation substrate was shown by two-dimensional polyacrylamide gel electrophoresis to be G21k, a low-molecular-weight GTP-binding protein (G protein) suggested previously by us to be involved in PLC regulation [Wang, P. et al. (1987) J. Biochem. 102, 1275-1287; (1988) 103, 137-142; and (1989) 105, 461-466], and the other major ADP-ribosylation substrate was identified as a rho A protein. Under the experimental conditions of the IPs formation study, ADP-ribosylation of both G21k and rho A proteins by botulinum ADP-ribosyltransferase in membranes and permeabilized cells was observed. These results suggest that botulinum ADP-ribosyltransferase-induced PLC stimulation in thymocytes is closely correlated with ADP-ribosylation of the low-molecular-weight G proteins.
...
PMID:Low-molecular-weight GTP-binding proteins serving as ADP-ribosylation substrate for ADP-ribosyltransferase from Clostridium botulinum and their relation to phosphoinositides metabolism in thymocytes. 196 61

The effects of sodium fluoride upon basal and agonist-stimulated inositol phospholipid breakdown have been investigated in rat brain miniprisms. NaF concentration dependently increased basal inositol phospholipid breakdown, with a maximum effect being seen at 20 mM. NaF reduced the inositol phospholipid breakdown responses to stimulation by carbachol, noradrenaline, serotonin and quisqualate, but not to the stimulation produced by raising the assay [K+] from 6 to 18 mM. More detailed study demonstrated NaF to have a 'levelling' effect, reducing all InsP/(Lipid + InsP) values greater than 0.15 (i.e. produced by carbachol at raised [K+], noradrenaline and by 50 mM K+) to about this value. Time-course experiments indicated that NaF treatment reduced the rate of carbachol-stimulated inositol phospholipid breakdown up to this InsP/(Lipid + InsP) level and thereafter blocked further breakdown. Inhibitory effects upon carbachol-stimulated inositol phospholipid breakdown were not seen with forskolin, sodium nitroprusside or 8BrcGMP. Under conditions where there is no de novo synthesis of phosphoinositides from [3H]myo-inositol, NaF reduced the total Lipid + InsP labelling by about 20%. NaF in addition inhibits the activity of Ins(1,4)P2-phosphatase in cerebral cortical homogenates. It is concluded that fluoride ions inhibit agonist-stimulated inositol phospholipid breakdown via actions not only on G-proteins but also on phosphoinositide-specific phospholipase C substrate availability.
...
PMID:Multiple actions of fluoride ions upon the phosphoinositide cycle in the rat brain. 196 44

Langendorff perfusion of guinea pig hearts with phorbol 12-myristate, 13-acetate or 1,2-dioctanoylglycerol caused a progressive impairment of contraction and relaxation of the left ventricle. Exposure of the hearts to 4 microM phorbol 12-myristate, 13-acetate or 200 microM 1,2-dioctanoylglycerol for 3 minutes resulted in a redistribution of protein kinase C activity and increased phosphorylation of a 28 kDa cytosolic protein. Examination of the incorporation of [32P]Pi into phosphatidylinositols and inositoltrisphosphates, under identical conditions, revealed that the degree of 32P-labeling of phosphatidylinositol, phosphatidylinositol 4-monophosphate and phosphatidylinositol 4.5-bisphosphate was significantly increased. However, the degree of phosphate labeling of inositol trisphosphates was decreased. The effects of phorbol 12-myristate, 13-acetate and 1,2-dioctanoylglycerol on the intermediates of the phosphatidylinositol cycle were observed in the presence of prazosin, propranolol and atropine. Examination of the activity of phosphoinositide-specific phospholipase C in the perfused guinea pig hearts revealed that treatment with phorbol 12-myristate, 13-acetate was associated with a decrease in the membrane-associated enzymatic activity, assayed at low concentrations of calcium. Control hearts, perfused with a phorbol ester (4 alpha-phorbol 12,13-didecanoate) which does not activate protein kinase C, did not show any changes in cardiac contraction and relaxation or in the intermediates of the phosphatidylinositol cycle. The findings suggest that the basal production of inositol phosphates may be down-regulated by agents which activate protein kinase C in guinea pig hearts.
...
PMID:The effect of phorbol esters and diacylglycerol analogues on the basal phosphoinositide turnover in isolated guinea pig hearts. 196 45

Electropermeabilized human platelets containing 5-hydroxy[14C]tryptamine ([14C]5-HT) were suspended in a glutamate medium containing ATP and incubated for 10 min with (in various combinations) Ca2+ buffers, phorbol 12-myristate 13-acetate (PMA), guanine nucleotides, and thrombin. Release of [14C]5-HT and beta-thromboglobulin (beta TG) were used to measure secretion from dense and alpha-granules, respectively. Ca2+ alone induced secretion from both granule types; half-maximal effects were seen at a -log [Ca2+ free] (pCa) of 5.5 and maximal secretion at a pCa of 4.5, when approximately 80% of 5-HT and approximately 50% of beta TG were released. Addition of PMA, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), GTP, or thrombin shifted the Ca2+ dose-response curves for secretion of both 5-HT and beta TG to the left and caused small increases in the maximum secretion observed. These results suggested that secretion from alpha-granules, like that from dense granules, is a Ca(2+)-dependent process stimulated by the sequential activation of a G-protein, phospholipase C, and protein kinase C (PKC). However, high concentrations of PMA and GTP gamma S had distinct effects in the absence of Ca2+ (pCa greater than 9); 100 nM PMA released approximately 20% of platelet 5-HT but little beta TG, whereas 100 microM GTP gamma S stimulated secretion of approximately 25% of each. Simultaneous addition of PMA greatly enhanced these effects of GTP gamma S. Phosphorylation of pleckstrin in permeabilized platelets incubated with [gamma-32P]ATP was used as an index of the activation of PKC during secretion. In the absence of Ca2+, 100 nM PMA caused maximal phosphorylation of pleckstrin and 100 microM GTP gamma S was approximately 50% as effective as PMA; neither GTP gamma S nor Ca2+ enhanced the phosphorylation of pleckstrin caused by 100 nM PMA. These results indicate that, although activation of PKC promoted secretion, GTP gamma S exerted additional stimulatory effects on secretion from both dense and alpha-granules that were not mediated by PKC. Measurement of [3H]inositol phosphate formation in permeabilized platelets containing [3H]phosphoinositides showed that GTP gamma S did not stimulate phosphoinositide-specific phospholipase C in the absence of Ca2+. It follows that in permeabilized platelets, GTP gamma S can both stimulate PKC and enhance secretion via G-protein-linked effectors other than this phospholipase.
...
PMID:Factors affecting dense and alpha-granule secretion from electropermeabilized human platelets: Ca(2+)-independent actions of phorbol ester and GTP gamma S. 196 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---