Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phospholipid base exchange activity using choline as substrate was detected in plasma membranes (PM) and other subcellular fractions of rat liver, with microsomes (MS) showing the highest specific activity. In contrast, phospholipase D activity was only detected in PM. In PM, choline exchanged for phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS), whereas ethanolamine exchanged for PE and PS, and serine exchanged for PS. Ca2+ (10 microM or higher) stimulated choline incorporation into PC in MS and PM, whereas Mg2+ (10 microM or higher) stimulated it only in PM. Ethanolamine and serine incorporation into PM phospholipids was also stimulated by Ca2+, and inositol incorporation by Mn2+. Phospholipase D activity was substantial in the presence of EGTA and was slightly stimulated by Ca2+ concentrations less than 500 microM. It was undetectable without Mg2+. Low concentrations of oleate (1 mM or less) stimulated phospholipase D activity. These concentrations inhibited choline base exchange activity, whereas higher concentrations (3-8 mM) were stimulatory. Comparison of the subcellular distribution and Ca2+, Mg2+, and oleate effects on choline base exchange and phospholipase D activities supports the view that they are catalyzed by different enzymes. The incorporation of choline, but not ethanolamine or serine, into the phospholipids of PM, but not MS, was stimulated by micromolar concentrations of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) and other slowly hydrolyzable analogues of GTP. GDP, GMP, and other nucleoside triphosphates and their analogues were ineffective. GTP gamma S stimulation of base exchange activity was dependent upon Mg2+ and was inhibited by high concentrations of guanosine 5'-O-2-(thio)diphosphate. In the presence of low concentrations of GTP gamma S, ATP and its slowly hydrolyzable analogues stimulated base exchange activity. Dose-response curves for these nucleotides revealed a potency order consistent with mediation by purinergic receptors of the P2Y type. Base exchange activity stimulated by ATP plus GTP gamma S or GTP gamma S alone was not altered by treatment with pertussis or cholera toxins. These results suggest that the choline base exchange activity of liver PM is regulated by a pertussis toxin-insensitive G-protein linked to P2Y purinergic receptors.
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PMID:Phospholipid base exchange activity in rat liver plasma membranes. Evidence for regulation by G-protein and P2y-purinergic receptor. 131 19

Phospholipase D (PLD) can be activated by a variety of receptor agonists in different cell types. However, an effect of prostaglandins (PGs) on the activity of this enzyme has not been demonstrated previously. In this study, we found that PGE1 could stimulate PLD in human erythroleukemia cells, as measured by phosphatidylethanol formation, with an ED50 of 3.5 x 10(-7) M. PGE2 was also active, but other PGs including prostacyclin, PGD2 and PGF2, had no effect. PGE1 also elicited cyclic AMP production over the same concentration range that activated PLD. However, it is unlikely that cyclic AMP per se is responsible for PGE-induced PLD activation, because PLD could be substantially activated by PGE2 at concentrations (0.1-1 microM) which did not stimulate cyclic AMP production. Furthermore, no increase of phosphatidylethanol formation could be observed when cells were treated with other adenylyl cyclase-activating agents such as prostacyclin, forskolin and vasoactive intestinal peptide. In Ca+(+)-free medium, PLD activation by PGE1 and PGE2 was greatly reduced, indicating that their effect was through a Ca+(+)-dependent pathway. Pretreatment of cells with pertussis toxin abolished PGE1- and PGE2-stimulated PLD activity, implying the involvement of a G protein in the PGE-mediated signal transduction pathway. Our results not only indicate that E-series PGs may initiate some of their cellular effects through a novel pathway, activation of PLD, but also suggest that PGE-stimulated PLD activity in human erythroleukemia cells is Ca+(+)-dependent and is regulated via a pertussis toxin-sensitive G protein.
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PMID:Activation of phospholipase D by E-series prostaglandins in human erythroleukemia cells. 165 Aug 37

Activation of adenosine A1-, bradykinin- or P2U-receptors on DDT1 MF-2 smooth muscle cells all increased the formation of inositol 1,4,5-trisphosphate and the mobilization of intracellular calcium. All three types of agents could increase [Ca2+]i in the same cell. Activation of the P2U receptor with ATP or UTP produced larger responses than activation of bradykinin- and adenosine A1-receptors, with bradykinin and N6-cyclopentyladenosine. When agonist-stimulated levels of diacylglycerol were determined, all agonists caused biphasic changes of similar magnitudes. If anything, ATP and UTP tended to give larger increases in the second phase of stimulation. Phospholipase D, measured as the formation of phosphatidylethanol in cells labeled with [3H]palmitic acid and activated in the presence of ethanol, was activated similarly as phospholipase C, i.e. ATP or UTP caused the largest increase in phosphatidylethanol formation, followed by N6-cyclopentyladenosine and bradykinin which caused weaker responses. Activation of PLD by P2U receptors was pertussis toxin insensitive. The activation of PLD by the agonists was only weakly affected by a PKC inhibitor, Ro 31-7549 (3-[1-(3-aminopropanyl)-3- indolyl]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione). In contrast, ATP or UTP did not activate protein kinase C, determined in a permeabilized cell assay using two specific protein kinase C substrates, whereas N6-cyclopentyladenosine and bradykinin caused a substantial activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of phospholipase C and phospholipase D by stimulation of adenosine A1, bradykinin or P2U receptors does not correlate well with protein kinase C activation. 777 Jan 1

Phospholipase D (PLD) is an enzyme which participates in the signaling mechanism cleaving phosphatidylcholine (PC) to choline and phosphatidic acid (PA). In Tetrahymena pyriformis GL this enzyme activity is enhanced by different kinds of agonists (sodium orthovanadate, sodium fluoride and phorbol 12-myristate 13-acetate), and its activity can be inhibited by inhibitors such as pertussis toxin, calphostin C, genistein, trifluoperazine. These results suggest that the PLD signalling pathway is connected with the tyrosine kinase, phospholipase C, phosphatidylinositol and G-protein coupled signalling pathways. By demonstrating the PLD activity in Tetrahymena our knowledge on the signaling mechanisms at a unicellular level has been extended. The results support our view that most transducing mechanisms that are characteristic of mammalian cells are also in the protozoan Tetrahymena.
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PMID:Phospholipase D activity in the Tetrahymena pyriformis GL. 907 38

Phospholipase D (PLD) is activated in mammalian cells in response to a variety of growth factors and may play a role in cell proliferation. Lysophosphatidic acid (LPA) is a bioactive metabolite potentially generated as a result of PLD activation. Two human prostate cancer cell lines, PC-3 and LNCaP, express membrane PLD activity. The effects of LPA on PLD activity and proliferation were examined in PC-3 cells, which express hPLD1a/1b. Phorbol 12-myristate 13-acetate (PMA) induced a prolonged activation of PLD, as detected in both intact cells and membranes. LPA induced a transient activation of PLD that was maximal by 10 minutes. The EC50 for LPA-induced PLD activation was approximately 1 microM. Pertussis toxin did not inhibit activation of PLD by LPA or PMA. Ro-31-8220 and bisindolylmaleimide I, inhibitors of protein kinase C, blocked activation by PLD by both PMA and LPA. PMA-induced activation of PLD did not appear to require translocation of PLDs from cytosol to membrane. LPA stimulated proliferation of PC-3 cells with an EC50 of approximately 0.2 microM; this response was not inhibited by pertussis toxin. Perillyl alcohol, an anti-cancer drug, reversibly inhibited proliferation in response to either serum or LPA but did not inhibit activation of PLD by PMA or LPA. These data establish that LPA activates PLD and stimulates proliferation via Gi-independent pathways in a human prostate cancer cell line.
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PMID:Lysophosphatidic acid stimulates phospholipase D activity and cell proliferation in PC-3 human prostate cancer cells. 942 12

Amyloid beta protein is the major protein component of neuritic plaques found in the brain of Alzheimer's disease. The activation of phospholipase D by amyloid beta protein (25-35), quisqualate and phorbol 12, 13-dibutyrate was investigated in LA-N-2 cells by measuring phosphatidylethanol formation. The activation of phospholipase D by quisqualate and APP (25-35) was calcium-independent. The AbetaP (25-35) and quisqualate activation of phospholipase D appeared to be mediated through a pertussis toxin-sensitive GTP-binding protein. Phospholipase D activation by AbetaP (25-35), quisqualate and phorbol dibutyrate was not blunted by the protein kinase C inhibitors, staurosporine, H-7 and RO-31-8220. However, it was abolished by overnight exposure to phorbol dibutyrate. This activation of phospholipase D was prevented by the tyrosine kinase inhibitor, genistein but not by tyrophostin A. Several excitatory amino acid antagonists were tested for their ability to prevent the phospholipase D activation by quisqualate and AbetaP (25-35). Only NBQX was effective with an IC50 of 75 microM for AbetaP (25-35) and quisqualate. Activation of phospholipase D by AbetaP or quisqualate was absent in LA-N-2 cells previously desensitized by quisqualate or AbetaP (25-35), but the activation by phorbol dibutyrate was unaltered. The responsiveness to AbetaP and quisqualate in previously desensitized cells reappeared subsequent to a period of resensitization. The observations with the antagonist NBQX, and the desensitization and resensitization experiments, are consistent with a receptor occupancy mediated activation of phospholipase D by quisqualate and by AbetaP (25-35).
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PMID:Activation of LA-N-2 cell phospholipase D by amyloid beta protein (25-35). 980 77

Phospholipase D (PLD) is present in human placental tissue. Since purinergic receptor agonists activate PLD in many different cell types, we evaluated the purinergic activation of the enzyme in cultured trophoblasts from the placenta. We found that P(2) receptor agonists stimulate PLD. The preferred ligand for P(2X7) (P(2Z)) receptor subtype, BzBz-ATP (10(-3)M ), induced the enzyme more than ten times over basal (unstimulated) activity, while ATP caused a much smaller increase. ATPgammaS, ADP and UTP were even less effective, compared to BzBz-ATP or ATP. AMP and alpha,beta-methyl-ATP, a P(2X) agonist that is uniquely inactive on the P(2X7) subtype, had no effect. This represents the first suggestion of the presence of the P(2X7) type of receptor in human trophoblasts that was directly confirmed by immunoblot detection. The action of BzBz-ATP was dependent upon the presence of calcium in the culture medium and was inhibited by high (5m M ) Mg(++) concentration. P(2X7) receptor subtype specific antagonists, ATP-2',3'-dialdehyde (o-ATP), CBB and the broad specificity P(2) inhibitor PPADS inhibited the effect of BzBz-ATP. Pertussis toxin treatment did not inhibit the effect. Down-regulation of cPKC/nPKC isoforms by prolonged PMA treatment (36 h, 10(-7)M ) prevented the stimulation of PLD by P(2) agonists or the calcium ionophore A-23187. PLA(2) inhibitors did not block the effect of BzBz-ATP. The possibility for a calcium influx related interdependence of PLC and PLD was evaluated. For PLC activation, UTP and ATP surpassed BzBz-ATP, while ionophore did not elevate PLC (assessed by IP(3) measurements). This suggested the predominance of a P(2Y2) receptor in the whole cell in gross activation of PLC. PLD was affected with a reversed order of potency. These results and the dependence of PLD on PKC activity implies that a restricted, membrane localized calcium flux activates PKC and in turn, mediates the P(2X7) dependent stimulation of PLD. This may have implications for physiologic regulation of trophoblast function.
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PMID:Regulation of phospholipase D in human placental trophoblasts by the P(2) purinergic receptor. 1236 78

Photoreceptor cells contain rod outer segments (ROS) which are specialized light-sensitive organelles. The biological function of ROS is to generate a photoresponse, which occurs via the classic transducin-mediated pathway. Moreover, ROS undergo light-regulated membrane turnover and protein translocation whose mechanisms have not been fully elucidated to date. Phospholipase D (PLD) is a key enzyme involved in lipid signal transduction and membrane trafficking. We have previously reported that PLD activity is present in purified ROS (Salvador, G.A., Giusto, N.M., 1998. Characterization of phospholipase D activity in bovine photoreceptor membranes. Lipids 33, 853-860). We now demonstrate that ROS PLD activity is enhanced by phosphatidylinositol bisphosphate (PIP2) and cytosolic factors in a GTP dependent-manner. Western blot analysis demonstrates the presence of PLD1 isoform in purified ROS. In ROS obtained from dark-adapted retinas (DROS), PIP2-dependent PLD activity was higher than that observed in ROS obtained from light-adapted retinas (LROS). In addition, experiments carried out in the presence of C3 toxin inhibited PLD activity from DROS whereas pertussis toxin did not affect the enzyme activity. Western blot analysis demonstrates the presence of RhoA, a PLD upstream-regulator. Moreover, RhoA levels were higher in DROS with respect to those in LROS. The present study reports evidence of the involvement of the small G-protein, RhoA, in ROS PLD regulation. Our data strongly suggest that RhoA regulates ROS PLD activity under a light-dependent mechanism.
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PMID:Phospholipase D from photoreceptor rod outer segments is a downstream effector of RhoA: evidence of a light-dependent mechanism. 1663 Jun 12